Chemistry Reference
In-Depth Information
General procedure for the preparation of bromoalkyl chloroformates and carbamates.
[405]:
Bromoalkyl chloroformates of type 572: A solution of phosgene (3.25 g,
0.032 mol) (for a safe source, see Chapter 7) in dichloromethane (15 mL) was cooled
to
15
C under a nitrogen atmosphere. A solution of the appropriate alcohol
(0.016 mol) in dichloromethane (5 mL) was then added, followed by a solution of
pyridine (1.44 g, 0.018 mol) in dichloromethane (15 mL). The reaction mixture
was allowed to warm to room temperature and was stirred overnight. Nitrogen was
then passed through the solution to remove excess phosgene, and the solution was
washed successively with ice-cold water, ice-cold 5% NaHCO
3
solution, and ice-
cold water. After drying over MgSO
4
, the solvent was removed by distillation over a
water bath with the aid of a water aspirator, and unless noted otherwise, the resi-
due was distilled in vacuo to give the chloroformate. The product was examined
spectroscopically (IR, NMR) and then used without further purification for con-
version to the corresponding carbamate. Three chlorides were prepared: 1-bromo-
2-methyl-2-butyl chloroformate (55%, bp 53
C/0.1 mmHg), 1-bromo-2,3-dimethyl-
2-butyl chloroformate (62%, bp 34
C/0.15 mmHg), and 3-(bromomethyl)-3-pentyl
chloroformate (20%, bp 54
C/0.19 mmHg (dec.)).
Carbamates of type 573: A solution of the appropriate chloroformate (25 mmol)
in benzene (100 mL) was stirred at room temperature. To this was added dropwise
a solution of the amine (50 mmol) in benzene (50 mL) over a period of 30 min.
After stirring for 1 h, the precipitated salt was filtered off and washed with a small
amount of benzene. The solvent was removed in vacuo (20 mmHg) at 45
C from
the combined filtrate and washings, to leave the carbamate as an oily residue,
which was recrystallized from Skelly B. Results are collected in Table 4.23.
For a detailed presentation of other haloalkyl chloroformate syntheses using
phosgene equivalents, see Section 4.2.1 ''Chloroformylation''.
N-Carbobenzoxy-dl-serine benzyl ester 575 was converted to several O-(substi-
tuted carbamyl)-N-carbobenzoxyserine benzyl esters, either by condensation with
Tab. 4.23.
Carbamates 574 prepared with
-halo-tert-alkyl chloroformates [405].
a
O
R'
R"
R
X
N
H
O
574
R
RO
RP
X
Yield, %
mp, ˚C
C
6
H
5
Me
Et
Br
46
65
p-ClC
6
H
4
Me
Et
Br
53
77
cyclo-C
6
H
11
Me
Et
Br
64
80-80.5
C
6
H
5
Me
iPr
Br
65
66-66.5
p-ClC
6
H
4
Me
iPr
Br
67
86-87
cyclo-C
6
H
11
Me
iPr
Br
34
95
C
6
H
5
Et
Et
Br
47
61-62
cyclo-C
6
H
11
Et
Et
Br
70
98
C
6
H
5
Me
Et
OTs
55
77
