Chemistry Reference
In-Depth Information
of 3-cyano-3-cephem derivatives from readily available 7b-aminocephalosporanic
acid. The 7b-isocyanide 1634 is prepared by dehydration of the formylated 7b-
amino cephalosporanic acid derivative 1633 with phosphoryl chloride. Removal
of the 7b-isocyano group is carried out with tributyltin hydride and affords the
deaminated cephem derivative 1635 [1093].
H
2
N
S
S
N
OTBDMS
N
OTBDMS
O
O
84 %
1635
CO
2
CHPh
2
CO
2
CHPh
2
1632
HCO
2
H
Bu
3
SnH
benzene
reflux, 50 min
Ac
2
O
AIBN
H
OHC-HN
POCl
3
NC
S
S
lutidine
N
OTBDMS
N
OTBDMS
CH
2
Cl
2
O
O
CO
2
CHPh
2
4°C, 12 h
CO
2
CHPh
2
93 %
1633
52 %
1634
Typical procedure. Diphenylmethyl 7b-isocyano-3-tert-butyldimethylsilyloxymethyl-3-
cephem-4-carboxylate 1634 [1093]: To a solution of diphenylmethyl 7b-formamido-
3-tert-butyldimethylsiloxymethyl-3-cephem-4-carboxylate (1.0 g, 1.9 mmol) in di-
chloromethane (15 mL), 2,6-lutidine (0.81 mL, 7 mmol) and phosphoryl chloride
(0.22 mL, 2.3 mmol) were added at 0
C. After being kept at 4
C for 12 h, the
mixture was washed successively with 5% aqueous citric acid (15 mL), 5% aqueous
sodium hydrogen carbonate solution (15 mL), and saturated brine (15 mL). The
organic layer was dried over MgSO
4
and concentrated in vacuo. The residue
was chromatographed on Florisil (100-200 mesh, 20 g) eluting with dichloro-
methane to give a yellow oil. This was triturated with petroleum ether and filtered
to give diphenylmethyl 7b-isocyano-3-tert-butyldimethylsilyloxymethyl-3-cephem-4-
carboxylate 1634 as a yellow powder (450 mg, 52%); mp 93-95
C (dec.); [a]
25
D
¼
þ
29
:
5(c
¼
1, CHCl
3
).
Typical procedure. Diphenylmethyl 3-tert-butyldimethylsilyloxymethyl-3-cephem-4-carbo-
xylate 1635 (removal of the isocyano group) [1093]:
To a solution of diphenylmethyl
7b-isocyano-3-butyldimethylsilyloxymethyl-3-cephem-4-carboxylate 1634 (100 mg,
0.19 mmol) in benzene (1.0 mL), azobisisobutyronitrile (1.0 mg) and tributyltin
hydride (0.21 mL, 0.21 mmol) were added at room temperature. The mixture was
refluxed for 50 min and then the volatiles were evaporated in vacuo. The residue
was chromatographed on a silica gel column (4.5 g) eluting with dichloromethane
to give an oil, which on crystallization from hexane gave colorless crystals of di-
phenylmethyl 3-tert-butyldimethylsilyloxymethyl-3-cephem-4-carboxylate 1635 (79
mg, 84%); mp 105-110
C (dec.); [a]
25
D
¼þ
55
:
8(c
¼
1, CHCl
3
).
