Chemistry Reference
In-Depth Information
The isocyanate from 2-amino-2-trifluoromethyl succinic acid 1-ethyl ester 4-methyl
ester 457 was prepared in high yield using diphosgene in toluene [316].
CF
3
COO
O
O
NH
3
NCO
CCl
3
OCOCl
H
3
C
O
CH
3
H
3
C
O
CH
3
O
O
Toluene, 4h, 100°C
F
3
C
F
3
C
O
O
85 %
456
457
l-Aspartic acid esters 458 react with diphosgene in dioxane at 55
C to give the
corresponding isocyanate 459 in 62% yield [317].
2-Isocyanato-4-methyl-2-(trifluoromethyl)pentanecarboxylic acid methyl ester 461 was
prepared in 68% yield with diphosgene in dioxane [318].
CH
3
CH
3
NH
2
NCO
CCl
3
OCOCl
OCH
3
OCH
3
H
3
C
H
3
C
F
3
C
F
3
C
Dioxane
12h, 70 °C
O
O
racemate
460
68 %
461
Typical procedure. m-(Trifluoromethyl)phenylalanine methyl ester isocyanate [310]: Di-
phosgene (5.0 mL, 0.042 mol) was added to a suspension of m-(trifluoromethyl)
phenylalanine methyl ester hydrochloride (8.51 g, 0.03 mol) in dry dioxane (75 mL)
under nitrogen. The reaction mixture was refluxed overnight under an e
cient
hood, with the use of a gas trap (300 mL of 20% aqueous NaOH). Subsequent re-
moval of the solvent in vacuo, followed by vacuum distillation of the oily residue,
yielded 6.9 g (85%) of the pure isocyanate.
b-(Ethoxycarbonyl)ethyl isocyanate 463 was prepared by heating the b-alanine
ethyl ester hydrochloride 462 with diphosgene in the presence of active charcoal in
toluene (71.2% yield). Similarly, a-methoxycarbonyl-b-methylbutyl isocyanate was
obtained by treating l-leucine methyl ester hydrochloride with diphosgene in tol-
uene (69.7% yield) [319].
