Chemistry Reference
In-Depth Information
gene. The solvent was evaporated, and the colorless residue was placed in an ice
bath. It was treated with ethyl acetate (40 mL) followed by petroleum ether (90
mL). The product precipitated to give an isolated yield of 64 g (80-85%); mp 59-
61
C; [a]
22
D
¼
71.7 (c
¼
3.0, chloroform).
CO
2
Me
CO
2
Me
COCl
2
O
+
H
N
THF
60°C
2 h
O
H
2
N
CO
2
H
H
2
N
CO
2
H
O
x HCl
80-85 %
1162f
1163f
1164c
CO
2
H
H
CO
2
Me
H
2
N
O
aspartame
1165
Friedel-Crafts a-aminoacylation of aromatic compounds with several chiral N-
carboxy-a-amino acid anhydrides (NCAs) prepared with phosgene, triphosgene,
and PBr
3
has recently been reported [835, 836]. l-Proline-NCA 1163g was prepared
from proline 1162g with phosgene in ca. 100% yield. Pro-NCA 1163g reacts with
toluene to afford (S)-2-p-toluoylpyrrolidine hydrochloride 1167 [835].
O
1.
COCl
2
THF
4 h, 30°
C
H
CO
2
H
H
O
H
N
H
2. Ag
2
O
1 d, rt
AlCl
3
3 h, 2°C
O
x HCl
O
1162g
44 %
100 %
1163g
1167
Typical procedure.
l
-Pro-NCA 1163g [835]: Gaseous phosgene (for safe phosgenation,
see Chapter 7) was bubbled into a suspension of l-Pro 1162g (17.25 g, 150 mmol)
in THF (400 mL) for 4 h at ca. 30
C. The THF was then evaporated from the ho-
mogeneous solution to leave N-chlorocarbonyl-l-proline (N-COCl-l-Pro) as a yellow
oil. To a solution of N-COCl-l-Pro (35.7 g, 150 mmol) in acetone (400 mL) were
added Ag
2
O (20.4 g, 88 mmol) and Norit A (4.5 g) and the mixture was stirred for
at room temperature for 1 d. The mixture was then filtered from the black Norit
A and the THF (could be acetone, see above; the author) was evaporated to afford
