Acetic Acid → (3S,4S)-4-[(1R)-2-{(2S,4S)-1-allyloxycarbonyl-2-(2-fluoroethyloxymethyl)pyrrolidin-4-yl-thio}-1-methyl-2-oxoethyl]-3-{(1R)-1-(t-butyldimethylsilyl-oxy)ethyl}-2-azetidinone

HRID 703590Notes

Reaction equation

HRID 703590 reaction equation
[Si:1]([O:8][C@@H:9]([C@@H:11]1[C@@H:14]([C@@H:15]([CH3:24])[C:16](=[O:23])N2CCSC2=S)[NH:13][C:12]1=[O:25])[CH3:10])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH2:26]([O:29][C:30]([N:32]1[CH2:36][CH:35]([SH:37])[CH2:34][CH:33]1[CH2:38][O:39][CH2:40][CH2:41][F:42])=[O:31])[CH:27]=[CH2:28].C(N(CC)CC)C.C(O)(=O)C>O1CCCC1>[CH2:26]([O:29][C:30]([N:32]1[CH2:36][C@@H:35]([S:37][C:16](=[O:23])[C@@H:15]([C@H:14]2[NH:13][C:12](=[O:25])[C@@H:11]2[C@H:9]([O:8][Si:1]([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3])[CH3:10])[CH3:24])[CH2:34][C@H:33]1[CH2:38][O:39][CH2:40][CH2:41][F:42])=[O:31])[CH:27]=[CH2:28]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 14071070(3S,4R)-3-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-4-{(1R)-1-methyl-2-oxo-2-(2-thioxothiazolidin-3-yl)ethyl]-2-azetidinoneHCID 190870681-Allyloxycarbonyl-2-(2-fluoroethyloxymethyl)-4-mercaptopyrrolidine

Product 1

HCID 86744487(3S,4S)-4-[(1R)-2-{(2S,4S)-1-allyloxycarbonyl-2-(2-fluoroethyloxymethyl)pyrrolidin-4-yl-thio}-1-methyl-2-oxoethyl]-3-{(1R)-1-(t-butyldimethylsilyl-oxy)ethyl}-2-azetidinoneYield 42.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3S,4R)-3-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]- 4-{(1R)-1-methyl-2-oxo-2-(2-thioxothiazolidin-3-yl)ethyl]-2-azetidinone (3.17 g) in tetrahydrofuran (30 ml) were added 1-allyloxycarbonyl-2-(2-fluoroethyloxymethyl)-4-mercaptopyrrolidine (2.21 g) and triethylamine (1.46 ml) at 5° C., and the mixture was stirred at room temperature for 8.5 hours. Acetic acid (0.63 ml) was added to the mixture and the mixture was evaporated. The residue was dissolved in water and ethyl acetate. The organic layer was separated, washed with water, dried and evaporated. The residue was purified by chromatography on silica gel eluting with a mixture of dichloromethane and ethyl acetate (2:1 V/V) to give (3S,4S)-4-[(1R)-2-{(2S,4S)-1-allyloxycarbonyl-2-(2-fluoroethyloxymethyl)pyrrolidin-4-yl-thio}-1-methyl-2-oxoethyl]-3-{(1R)-1-(t-butyldimethylsilyl-oxy)ethyl}-2-azetidinone (1.82 g).

Workup

  1. customthe mixture was evaporated
  2. dissolutionThe residue was dissolved in water
  3. customThe organic layer was separated
  4. washwashed with water
  5. customdried
  6. customevaporated
  7. customThe residue was purified by chromatography on silica gel eluting with a mixture of dichloromethane and ethyl acetate (2:1 V/V)

Sources & evidence

ORD record
ord-6c308863892e4e06947e8d7c752d0899
Source dataset
uspto-grants-1991_01
Patent number
US04983596

Reaction notes

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