Chloroacetyl chloride → 2-Benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-(2-chloroacetamido-thiazol-5-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

HRID 2413441Notes

Reaction equation

HRID 2413441 reaction equation
[Cl:1][CH2:2][C:3](Cl)=[O:4].[NH2:6][C:7]1[S:8][C:9]([C:12]2[CH2:19][S:18][CH:17]3[N:14]([C:15](=[O:28])[CH:16]3[NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:13]=2[C:29]([O:31][CH:32]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:30])=[CH:10][N:11]=1.C(N(CC)CC)C>O1CCCC1.C(=O)(O)[O-].[Na+]>[CH:32]([O:31][C:29]([C:13]1[N:14]2[CH:17]([S:18][CH2:19][C:12]=1[C:9]1[S:8][C:7]([NH:6][C:3](=[O:4])[CH2:2][Cl:1])=[N:11][CH:10]=1)[CH:16]([NH:20][C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[C:15]2=[O:28])=[O:30])([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1

Participants

6

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 131759453-(2-Aminothiazol-5-yl)-2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

Product 1

HCID 133196212-Benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-(2-chloroacetamido-thiazol-5-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-eneYield 54.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

Chloroacetyl chloride (12.37 g) is added to a solution of 3-(2-amino-thiazol-5-yl)-2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (60 g) in tetrahydrofuran (350 cc) cooled to 0° C., and triethylamine (16.3 cc) is then added in 6 minutes. After 1 hour at 0° C., the reaction mixture is diluted with a half-saturated sodium bicarbonate solution (800 cc) and extracted with ethyl acetate (3×200 cc). The combined organic phases are washed with a saturated sodium chloride solution (250 cc) and dried, after which they are concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. to give an orange froth (78 g) which is recrystallised from acetonitrile (300 cc) to give cream crystals (37.4 g) of 2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-(2-chloroacetamido-thiazol-5-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

Workup

  1. extractionextracted with ethyl acetate (3×200 cc)
  2. washThe combined organic phases are washed with a saturated sodium chloride solution (250 cc)
  3. customdried
  4. concentrationafter which they are concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C.
  5. customto give an orange froth (78 g) which
  6. customis recrystallised from acetonitrile (300 cc)

Sources & evidence

ORD record
ord-4b7264f4f0b94a0c80de7519f336035c
Source dataset
uspto-grants-1985_01
Patent number
US04496560

Reaction notes

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