Organic Chemistry of Drug Synthesis. Volume 7

with ethyl chloroformate ( 57 ). The benzyl carbamate function on nitrogen
at the 4 position is next removed by reduction with ammonium formate
over palladium to afford the primary amine 58 ; this compound is then
resolved as its dibenzyl tartrate salt to afford the (2R,4S) isomer.
Reductive amination with the bis(trifuoromethyl benzaldehyde) ( 59 )in
the presence of sodium triacetoxy borohydride. Acylation with methyl
chloroformate completes the synthesis of 60.^11

F 3 C

NH 2

+ O=HC

N

N

NN

NH

52

53 F^3 C

NH

N

54

HN

O

OCH^2 C^5 H^5

O

NH

F 3 C

HN OCH^2 C^6 H^5

O

56

55

N

F 3 C

HN OCH^2 C^6 H^5

O

C 2 H (^5) O O
ClCO 2 C 2 H 5
57
N
F 3 C
NH 2
C 2 H (^5) O O
58

1. HCO 2 – NH 4 +
   Pd
   2. Resolve

CF 3

CF 3

O=HC CF 3

CF 3

1.

N

F 3 C

N

C 2 H (^5) O O
O
O
59
60

2. CH 3 OCOCl

H 3 C

As noted previously, anticholinergic agents have undergone something
of a renaissance due to their use as drugs to treat urinary incontinence. The
synthesis of one of these muscarinic antagonsists starts with the classic

HN O

61

POCl 3 N 1. NaBH 4

62

2. Resolve

NH

63

ClCO 2 C 2 H 5

N

64

OC 2 H 5

N^65 O

NaH

N

66

O

O

N

HO

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