3-Chloro-2,2-dimethylpropanoyl chloride → p-Nitrobenzyl 2-(4-tert-butylthio-2-oxo-1-azetidinyl)-5-chloro-4,4-dimethyl-3-oxopentanoate

HRID 2371895Notes

Reaction equation

HRID 2371895 reaction equation
C[Si]([NH-])(C)C.C[Si]([NH-])(C)C.[Li+].[Li+].[C:13]([S:17][CH:18]1[N:21]([CH2:22][C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=2)=[O:24])[C:20](=[O:36])[CH2:19]1)([CH3:16])([CH3:15])[CH3:14].[Cl:37][CH2:38][C:39]([CH3:44])([CH3:43])[C:40](Cl)=[O:41]>C1COCC1.C1(C)C=CC=CC=1.Cl.[Na+].[Cl-]>[C:13]([S:17][CH:18]1[N:21]([CH:22]([C:40](=[O:41])[C:39]([CH3:44])([CH3:43])[CH2:38][Cl:37])[C:23]([O:25][CH2:26][C:27]2[CH:28]=[CH:29][C:30]([N+:33]([O-:35])=[O:34])=[CH:31][CH:32]=2)=[O:24])[C:20](=[O:36])[CH2:19]1)([CH3:16])([CH3:14])[CH3:15]

Participants

8

Reactant 3

HCID 613453-Chloro-2,2-dimethylpropanoyl chlorideHCID 14460289p-Nitrobenzyl (4-tert-butylthio-2-oxo-1-azetidinyl)acetateHCID 86588160Lithim bis(trimethylsilylamide)

Product 1

HCID 14460305p-Nitrobenzyl 2-(4-tert-butylthio-2-oxo-1-azetidinyl)-5-chloro-4,4-dimethyl-3-oxopentanoateYield 69.4%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 1140TolueneSolventHCID 5234Sodium ChlorideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

6 ml of a 1M solution of lithium bis(trimethylsilylamide) in THF is slowly added dropwise to a stirred mixture, at 70° C., of 1.06 g (3 mmol) of p-nitrobenzyl 2-(4-tertbutylthio-2-oxo-1-azetidinyl)acetate and 410 μl (3.17 mmol) of chloropivaloyl chloride in 38 ml of absolute tetrahydrofuran, and the mixture is stirred for a further 30 minutes at -70° C. The reaction mixture is diluted with 250 ml of toluene, and 10 ml of 2N aqueous HCl and 100 ml of saturated NaCl solution are added. After separation, the organic phase is again washed with 100 ml of saturated NaCl solution then dried over MgSO4, and filtered, and the solvent is removed in vacuo on a rotary evaporator. The non-crystalline residue is chromatographed over 46 g of silica gel using toluene:ethyl acetate (19:1), to give 980 mg of non-crystalline title compound. IR in CH2Cl2 : 2930, 1770, 1760, 1725, 1615, 1530, 1465, 1370, 1250, 1215, 1190, 1110, 1040, 1000, 847 cm-1.

Workup

  1. additionare added
  2. customAfter separation
  3. washthe organic phase is again washed with 100 ml of saturated NaCl solution
  4. dry with materialthen dried over MgSO4
  5. filtrationfiltered
  6. customthe solvent is removed in vacuo on a rotary evaporator
  7. customThe non-crystalline residue is chromatographed over 46 g of silica gel

Sources & evidence

ORD record
ord-279b1b53757941a48299cb50d5acb403
Source dataset
uspto-grants-1992_03
Patent number
US05096899

Reaction notes

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