A convenient synthesis of optically pure (S,S)-norpseudoephedrine

Tetrahedron Letters,Vol.30,No.8,pp Printed in Great Britain

A CONVENIENT

SYNTHESIS

Armin Central Catalysis,

OF OPTICALLY

Boerner

0040-4039/89 $3.00 + .OO Perqamon Press plc

929-930,1989

and

PURE

(S, S) -NORPSEUDOEPHEDRINE

Hanswalter

Krause*

Division of

Institute of Organic Chemistry, GDR Academy of Sciences, 2500

Complex GDR

Restock,

The synthesis of optically pure (S,S)-norpseudoephedrine from (lS,2S)-2-amino-1(4-nitrophenyl)propan-l,3-diol We describe is

used

starting The

a convenient

in

appetite

from

chemistry

recently the

synthesis

an

intermediate

of

chloramphenicol

several

papers

N-acyl-L-base’ and 2 . Furthermore,

were

have

been

performed

amphenicol (0.1

by

they

%>.

primary

Treatment

of

the

and

Raney-nickel

mild

condition

nor

the

H2S04 be

vantage these for

for

complete,

no

the

to 3

Reaction

of

4

3-0-tosyl-ester

2

1,3-di-0-tosylate to

80

becomes

OC and the

the

to 1.1 (mp

to the

in

product.

the

the

p-TsCl 75

%)

in

molar

of of

929

the

OC,

tosyl

80

in

of

‘C)

the

inter-

aqueous hours

to

the

ad-

under yields

Cu-powder

mp 162-G

the

group

3

migrating

rising 3

and

Under

pure

reported

(R=H, (0

to

%).

underlines

addition

forming

the

phthalimido

required

the

.4

of

nitro

isopropa-

a rather‘

pyridine

p-TsCl

the

with

the

groups

however,

ratio

Replacement

acyl

without

conditions,

1)

This

to

The

choice

proceeded

Therefore,

chlor-

yield

moiety.

affording

giving

of

of

mp 136-7

observed.

N2

of

inter-

small

proper

Scheme

degree’.

of

D-base

very

the

procedure

overestimated.

OC,

in

efficiently

was

and

elucidation

only

contrast

evolution

equivalent

enhancing

of

neither

attacked

loss

be

these

photooxidation

on

(R=NH2,

which

high

170-4

to

(R=N02,

diazotization

A).

regard

substitution

hydrogenation were

group

seem

3 -

(L-base interest

1,2-aminoalcohol

2

amine

phthaloyl

under

main

the

transfer

a rather

led with

obtain

the

phthaloyl

rapidly

to

diazotization

Although

of

adjoining

group

NaN02.

2-benzamido’

ethanol

the

suitable

depend

the

form

Meerwein-Ponndorf-Verley 3 authors . Early investigations

but

for

rat.

of

recently by Czech 4 . During the structural

derivative5

yielded of

conditions

the

in

antiepilepticum

still

reactions of

difficulties

hydrogen

hydroxyl

nearly

al.

main

benzylic

with

with

which

a special synthesis

is

published

conversion

N-phthaloyl

the

compound as

norpseudoephedrine,

the

no1

mediate

et

title

chloramphenicol

amendments

important by

the

been

demanded

group

the

administered

intermediates

further

obtained

OH-group

of

some

Fodor

Obviously,

N-protection

and

have

mediate

reduction

of

suppressors

starting described.

is

and

OC,

provided

75

the

corresponding the

temperature

1,3-ditosylate by

iodide

in

5

%).

930

was

performed

the

reaction

rate

the

hydroxyl

group

which

with

became

afforded

revealed

ceeds

of

give

s

that

Among

the only

ephedrine

I was

References

2) 3) 4) 5) 6) 7)

8) 9)

OC,

phthaloyl

80

with also

group starting

or

other

pyridine,

(mp 8

179-83

of

‘C,

and

%),

the

nitro

group

pat,hway

in

bond

1

hydrazinolysis c=7,

H20;

investigated to

L-base.

It

be

useful

hydrogenation

suitable

for

in to

the

be

the

1 pro-

cited.

Treat-

cleavage

to

yielded

L-nor-

acetyl

, benzoyl,

norpseudo-

stable

processes,

halogen

with of

lit.

(alkyl,

proved

H2 expe-

combined iodide

ester

of

and

Preliminary

synthetic

Scheme

out

%).

the

after

groups

80

of

structure

corresponding

+42.6O,

catalytic

increasing acylation

the

((ar]t”

turned

90

*C,

only

which

with

highly

. Reduction of _6 with Pd/C

resulted

%),

thus

Simultaneously,

incorporation

under inert (Br

trans-

against instead

practised).

We are

and

HMPA.

indicating

N-protected

synthesis

Acknowledgment:

1)

thus

different the

6 -

methoxide

hydrochloride

hydrogenation

treatment of

give

dehalogenation

mp 156-8

anhydride,

DMSO or

mp 98-100.5 -7 (R=Ac, hydrogenation of the

the

potassium

pseudoephedrine

fer

to

alcohol

reductive

7 by (R=H,

acetic

to

from the spectra

disadvantageously,

ment

cbo)

boiling

occurs

amino

simultaneous

in

contrast

evident

the

riments

NaI in

grateful

to

Mrs.

G.

Voss

for

technical

assistance.

Notes:

Shenyang Yaoxueyan Xuebao 1986, 3, 121; C.A. 1987, Y. Xu and C. Yu, Z. Liu, 106, 196091e. N. M. Sanghavi and M. N. Trivedi, Indian Drugs 1986, 23, 310. P.R. Kamath, CS 231, 441 (1983, Inv.: J. Kostkan, J. Jary, M. Potacova, Czech, J. Nedbal and M. Maternova); C.A. 1987, 106, 18079z. J. Kiss and I. Sallay, J. ChemToc. 1951, 1858. G. Fodor, A. Terada, H. Ito and M. Nagawa, Sankyo Kenkyusho Nempo 1963, 42; -15, C.A. 1964, 60, 11924a. L. H. Welsh7J. Org. Chem. 1967, 32, 119. M. hl, Shemyakin, E, Al. Bamdas, E.T. Vinogradova, M. G. Karapetyan, M. N. Kolosov, A. C. Khokhlov, Yu. B. Shvetsov and L. A. Shukina, Dokl. qkad. Nauk SSSR 1952, 136, 565.. H-NMR (CDCl 9 1.77 (s, 3H), 3 37 (m., 2H), 4.86 (m, ItI), 6.25 (d, lH), 7.25-8.00 (m3 11H); IR (KBr)(cm-I) : 1780, 1745, 1719 (3 ) VV. N. Nagai and S. Kano, Justus Liebigs Ann. Chem. 1929, 174. -_’

%90*

(Received in Germany 14 Novem5er 1988)‘