N,O-bis(trimethylsilyl)acetamide → Benzhydryl 7-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-[3-chloro-1-propen-1-yl]-3-cephem-4-carboxylate

HRID 580212Notes

Reaction equation

HRID 580212 reaction equation
[NH2:1][CH:2]1[C:29](=[O:30])[N:4]2[C:5]([C:13]([O:15][CH:16]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:14])=[C:6]([CH:9]=[CH:10][CH2:11][Cl:12])[CH2:7][S:8][C@H:3]12.C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.Cl.[NH2:44][C:45]1[S:49][N:48]=[C:47]([C:50](=[N:54][O:55][CH3:56])[C:51](Cl)=[O:52])[N:46]=1>C(Cl)Cl>[NH2:44][C:45]1[S:49][N:48]=[C:47]([C:50](=[N:54][O:55][CH3:56])[C:51]([NH:1][CH:2]2[C:29](=[O:30])[N:4]3[C:5]([C:13]([O:15][CH:16]([C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)[C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)=[O:14])=[C:6]([CH:9]=[CH:10][CH2:11][Cl:12])[CH2:7][S:8][C@H:3]23)=[O:52])[N:46]=1

Participants

5

Reactant 3

HCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 736682632-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl chloride hydrochlorideHCID 131715606Diphenylmethyl 7-Amino-3-(3-chloro-1-propen-1-yl)-3-cephem-4-carboxylate

Product 1

HCID 131715608Benzhydryl 7-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-[3-chloro-1-propen-1-yl]-3-cephem-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of XVIII (Z isomer) (20 g, 42 mmole) in CH2Cl2 (420 ml) containing N,O-bis(trimethylsilyl)acetamide (34 ml, 125 mmole) was added 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl chloride hydrochloride (15.2 g, 59 mmole) in three portions over a period of 30 minutes at -10° to 0° C. The mixture was stirred for 30 minutes at 0°-5° C. and concentrated under reduced pressure. The residual brown oil was dissolved in ethyl acetate (420 ml) and the solution was washed successively with saturated aqueous NaHCO3 (3×15 ml), saturated aqueous NaCl (15 ml), 10% HCl (15 ml) and saturated aqueous NaCl (15 ml), and concentrated to about 50 ml of the volume. To the concentrate was added n-heptane (200 ml) to give 28.5 g (90% pure) of the title compound VIII-1 (Z-isomer) as a colorless powder. M.p. >150° C. (dec.).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residual brown oil was dissolved in ethyl acetate (420 ml)
  3. washthe solution was washed successively with saturated aqueous NaHCO3 (3×15 ml), saturated aqueous NaCl (15 ml), 10% HCl (15 ml) and saturated aqueous NaCl (15 ml)
  4. concentrationconcentrated to about 50 ml of the volume
  5. additionTo the concentrate was added n-heptane (200 ml)

Sources & evidence

ORD record
ord-281c613339dc4f6aa0aebd9b05d23bf2
Source dataset
uspto-grants-1988_06
Patent number
US04751295

Reaction notes

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