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

HRID 482932Notes

Reaction equation

HRID 482932 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].Cl.[NH:29]1[CH2:32][CH2:31][CH:30]1[C:33]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:34].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>ClCCl>[C:1]1([CH2:7][O:8][C:9]([NH:11][C@H:12]2[CH2:15][N:14]([C:24]([N:29]3[CH2:32][CH2:31][C@H:30]3[C:33]([O:35][CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[O:34])=[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 6371PhosgeneHCID 8471Triethylamine2×HCID 62657Potassium Phosphate, TribasicHCID 12834624benzyl N-[(3S)-2-oxoazetidin-3-yl]carbamateHCID 70081492Azetidine-2-carboxylic acid, benzyl ester hydrochloride

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

Conditions

Temperature
-5 °C

Procedure

A slurry of (S)-3-[[(phenylmethoxy)carbonyl]amino]-2-azetidinone (0.78 g, 3.54 mmole) in dry dichloromethane was warmed briefly to 50° C. and then cooled to -5° C. Triethylamine (0.354 g, 3.54 mmole) and phosgene (5.7 ml of 12.5% phosgene/toluene) were added and the reaction was stirred at -5° C. for 2 hours. The reaction was concentrated to a residue and fresh dichloromethane was added. After the solution was cooled to -50° C., triethylamine (0.714 g, 7.08 mmole) and azetidine-2-carboxylic acid, benzyl ester hydrochloride (0.8 g, 3.54 mmole) were added. The reaction was stirred at -5° C. for 45 minutes. The reaction mixture was poured into 10% monobasic potassium phosphate and the dichloromethane layer was separated and washed with water and brine. After drying over sodium sulfate the solvent evaporated. The crude oil was flash chromatographed on silica (LPS-1) eluting with ethyl/acetate:hexane (1:1). Fractions containing pure compound were concentrated to give 0.622 g of the title compound.

Workup

  1. concentrationThe reaction was concentrated to a residue and fresh dichloromethane
  2. additionwas added
  3. temperatureAfter the solution was cooled to -50° C.
  4. stirringThe reaction was stirred at -5° C. for 45 minutes
  5. customthe dichloromethane layer was separated
  6. washwashed with water and brine
  7. dry with materialAfter drying over sodium sulfate the solvent
  8. customevaporated
  9. customchromatographed on silica (LPS-1)
  10. washeluting with ethyl/acetate
  11. additionFractions containing pure compound
  12. concentrationwere concentrated

Sources & evidence

ORD record
ord-3f6fd980ca1f400faa0f9cb04919036e
Source dataset
uspto-grants-1986_03
Patent number
US04576749

Reaction notes

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