Chemistry Reference
In-Depth Information
(CCl
3
O)
2
CO
O
O
O
O
H
2
N
O
NH
2
OCN
O
NCO
1. Me
3
SiNEt
2
, (NH
4
)
2
SO
4
100°C, 24h, 40h reflux
2. MgO, CH
2
Cl
2
, 43h rt
378
379
To phosgenate tryptamine 380 in the presence of triethylamine, one-third of an
equivalent of triphosgene was added. When HBr/AcOH was added and the reac-
tion mixture was heated for a short time, the intermediate isocyanate cyclized spon-
taneously, affording the lactam in 74% yield in a one-pot reaction [268, 269].
1.
(CCl
3
O)
2
CO
, TEA
2. HBr or AlCl
3
N
NH
2
NH
R
R
R
C
O
H
H
H
O
R = H, OMe
380
381
382
Typical procedure. 2,3,4,9-Tetrahydro-1H-pyrido[3,4-b]indol-1-one 382 [268]:
Trypt-
amine 380 (9.0 g, 56.2 mmol) and triethylamine (13.8 g, 136.3 mmol) were dis-
solved in warm toluene (800 mL). Under vigorous stirring, a solution of tri-
phosgene (6.7 g, 22.6 mmol) in toluene (35 mL) was added dropwise and the
mixture was stirred for a further 20 min at room temperature. Then, HBr (30% in
acetic acid; 13 mL) was added and the mixture was refluxed for 30 min. After
cooling to room temperature, water (300 mL) and ethyl acetate (300 mL) were
added and, after separation of the layers, the aqueous phase was extracted once
more with ethyl acetate (300 mL). The combined organic layers were dried over
magnesium sulfate and concentrated in vacuo. The residue was recrystallized from
methanol/ethyl acetate (1:1) to afford 7.74 g (74%) of 2,3,4,9-tetrahydro-1H-pyr-
ido[3,4-b]indol-1-one 382 as a white solid; mp 184
C.
Chiral aliphatic isocyanates 384, which are applied to aminopropyl columns to
render them chiral for the resolution of racemic amines, alcohols, and acids as
amide, urea, carbamate or hydrazide derivatives, have been prepared with tri-
phosgene. The authors found that approximately 0.66 mol rather than 0.33 mol
of triphosgene was required per mol of amine, presumably because of a loss of
phosgene gas along with the HCl by-product [270].
Cl
R
(CCl
3
O)
2
CO
R
NCO
3
CH
3
Toluene, reflux, 7 h
CH
3
R = 4-NO
2
-Phenyl, Benzyl
384
383
