Chemistry Reference
In-Depth Information
lution was added dropwise under external cooling with ice/water over a period of
15 min to a solution of glycine (15 g, 200 mmol) in 1 n NaOH (200 mL). After
stirring for a further 1 h at room temperature, the mixture had a pH of about 8;
this was adjusted to 4-5 with 2 n H
2
SO
4
. The mixture was then concentrated in
vacuo and the residue was taken up in ethyl acetate/water. The aqueous phase was
separated, acidified to pH 1.5-2, and extracted twice with ethyl acetate. The com-
bined organic layers were washed with water, dried over sodium sulfate, and con-
centrated in vacuo. The residue was crystallized from diethyl ether/petroleum
ether. The crystals were dried in vacuo to afford 16.5 g (82%) of CyOC-Gly-OH 568;
mp 147-148.5
C.
H
3
C
H
3
C
COCl
2
,
CH
2
Cl
2
-70°C to rt
O
Cl
OH
NC
NC
CH
3
O
CH
3
566
567
N
H
3
C
H
2
N
COOH NaOH
1.
2. H
2
SO
4
O
COOH
NC
CH
3
O
82 %
568
The effect of structure on the ease of solvolytic deblocking of an array of a-
halo-tert-alkyl carbamates has been studied. The 1,3-dibromo-2-methyl-2-propyloxy-
carbonyl group (DB-t-Boc) is easily deblocked by warming in ethanol or methanol
and is therefore recommended as an acid-stable, solvolytically deblockable, amino
protecting group. The key chloroformate 572 was readily synthesized from meth-
allyl chloride 569 by conversion to methallyl bromide 570 followed by reaction with
hypobromous acid to give the bromohydrin 571 and treatment of the latter with
phosgene. Practical use of the DB-t-Boc group has been demonstrated by synthesis
of the dipeptide phenylalanylleucine [405].
Br
H
3
C
H
3
C
NBS
H
2
O / Me
2
SO
NaBr
acetone
OH
Cl
Br
Br
CH
2
CH
2
CH
3
569
570
571
COCl
2
Br
NH
2
Br
N
O
O
Cl
Br
Br
CH
3
O
CH
3
O
573
572
