Toluene → (S)-1-[[(S)-3-[[(Phenylmethoxy)carbonyl]amino]-2-oxo-1-azetidinyl]carbonyl]-2-azetidinecarboxylic acid, phenylmethyl ester

HRID 482933Notes

Reaction equation

HRID 482933 reaction equation
[C:1]1([CH2:7][O:8][C:9]([NH:11][C@H:12]2[CH2:15][NH:14][C:13]2=[O:16])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[C:24](Cl)(Cl)=[O:25].[CH2:28]1[C@@H:31]([C:32]([OH:34])=[O:33])[NH:30][CH2:29]1.[C:35]1([CH3:41])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>ClCCl>[C:1]1([CH2:7][O:8][C:9]([NH:11][C@H:12]2[CH2:15][N:14]([C:24]([N:30]3[CH2:29][CH2:28][C@H:31]3[C:32]([O:34][CH2:41][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[O:33])=[O:25])[C:13]2=[O:16])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 5

HCID 1140TolueneHCID 6371PhosgeneHCID 8471Triethylamine2×HCID 16486L-Azetidine-2-carboxylic acidHCID 12834624benzyl N-[(3S)-2-oxoazetidin-3-yl]carbamate

Product 1

HCID 86740685(S)-1-[[(S)-3-[[(Phenylmethoxy)carbonyl]amino]-2-oxo-1-azetidinyl]carbonyl]-2-azetidinecarboxylic acid, phenylmethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A slurry of (S)-3-[[(phenylmethoxy)carbonyl]amino]-2-azetidinone (0.44 g, 2 mmole) in 10 ml of dichloromethane was chilled to -10° C. under argon and treated with 0.3 g (3 mmoles) of triethylamine, followed by 3 ml (3.75 mmoles) of 12.5% phosgene in toluene. After 2 hours at -10° C., the mixture was evaporated in vacuo at 10° C., the residue taken up in 15 ml of dichloromethane at -10° C., and 0.4 g (4 mmole) of triethylamine was added followed by 0.45 g (2 mmole) of L-azetidine-2-carboxylic acid, phenylmethyl ester. After 30 minutes at 0° C., the reaction was extracted with 10% monobasic potassium phosphate and water, dried (sodium sulfate) and chromatographed on silica (LPS-1) (hexane:ethyl acetate, 1:1), to give the title compound (Rf=0.71 in ethyl acetate), 0.34 g.

Workup

  1. customthe mixture was evaporated in vacuo at 10° C.
  2. customtaken up in 15 ml of dichloromethane at -10° C.
  3. waitAfter 30 minutes at 0° C.
  4. extractionthe reaction was extracted with 10% monobasic potassium phosphate and water
  5. dry with materialdried (sodium sulfate)
  6. customchromatographed on silica (LPS-1) (hexane:ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-62ed91a3c79d4845826ed61e0670445c
Source dataset
uspto-grants-1986_03
Patent number
US04576749

Reaction notes

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