Chemistry Reference
In-Depth Information
O
O
O
O
NH
2
NCO
O
(CCl
3
O)
2
CO
O
O
HO
Cl
O
CH
2
Cl
2
, Py, 0°C
107
108
O
OMe
O
O
NH
O
MeOH
O
MeO
O
109
Typical procedure. Methyl 5
0
-[(methoxycarbonyl)oxy]-3
0
-oxospiro{1,3-dioxolane-2,7
0
-(3
0
H)-
[1,5][3]hexene[1,5]diyno[1H-2]benzopyran}-8
0
-yl carbamate 109 [60]:
Triphosgene
(1.01 g, 3.4 mmol) was added under nitrogen to a solution of vinyl amine 107
(365 mg, 1.17 mmol) in dry dichloromethane (80 mL) at 0
C. Pyridine (1.40 mL,
17.4 mmol) was then added, followed by methanol (10 mL). After 30 min at 0
C,
the reaction was quenched by the addition of pH 7 phosphate buffer (50 mL),
followed by ethyl acetate (200 mL). The aqueous layer was extracted with ethyl
acetate (3
50 mL). The combined organic layers were dried over MgSO
4
, fil-
tered, and concentrated in vacuo. The residue was subjected to flash chro-
matography on SiO
2
(hexanes/ethyl acetate, 2:3) to give 413 mg (82%) of
methyl 5
0
-[(methoxycarbonyl)oxy]-3
0
-oxospiro{1,3-dioxolane-2,7
0
-(3
0
H)-[1,5][3]hex-
ene[1,5]diyno[1H-2]benzopyran}-8
0
-yl carbamate 109 as a yellow solid; mp
105
C
>
(dec.).
Activation of 2-adamantol as chloroformate 111 using triphosgene and subse-
quent carbamate formation in the synthesis of a-methyltryptophan derivatives 112
as highly selective and orally active gastrin and CCK-B antagonists with potent
anxiolytic properties has also been reported [61].
H
N
H
N
2-Ad-OCOCl
111
*
*
COOMe
Me
COOMe
Me
H
2
N
2 -AdOC-HN
110
112
