Chemistry Reference
In-Depth Information
O
O
O
O
(CCl
3
O)
2
CO
NH
2
NCO
O
O
O
O
Et
3
N, Et
2
O, 0°C
O
O
O
O
95 %
468
469
Trimethylsilyl esters of C5
C6 branched a-amino acids and their enantiomers
470 have been converted into the corresponding isocyanates 471 with triphosgene
[322].
a
* HCl
NH
2
NCO
(CCl
3
O)
2
CO
O
O
Si
Si
CHCl
3
, iPr
2
EtN,
acetonitrile, 20 min, 15-22°C
O
O
470
471
A convenient method for the synthesis and derivatization of enantiopure a-iso-
cyanato carboxylic acid esters starting from a-amino acid esters has been devised
[314]. The isocyanates are obtained in enantiomerically pure form (
99% ee)bya
DMAP-catalyzed isocyanation with Boc
2
O, which proceeds in 10 min at room
temperature (for typical procedures employing Boc
2
O, see the Boc
2
O Section of the
present chapter). In situ derivatization of the isocyanates by reaction with amines
and alcohols affords the corresponding enantiopure ureas and carbamates. Methyl
esters of various amino acids 472 have been carbonylated by Boc
2
O at ambient
temperature [314].
>
NH
2
NCO
Boc
2
O
OCH
3
OCH
3
R
R
DMAP, CH
2
Cl
2
, 10 min, 25 °C
O
O
472
473
L-alanine Me ester yield 49 %
L-valine Me ester yield 91 %
L-isoleucine Me ester yield 90 %
L-leucine Me ester
yield 82 %
3-[2-Amino-3-(2-methoxycarbonylethoxy)-2-(2-methoxycarbonylethoxymethyl)propoxy]-
propionic acid methyl ester 474 was carbonylated with Boc
2
O at ambient temperature
[323].
11-Isocyanato-undecanoic acid methyl ester was prepared in 80% yield by carbon-
ylating 11-amino-undecanoic acid methyl ester with Boc
2
O [230].
