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

HRID 482928Notes

Reaction equation

HRID 482928 reaction equation
[NH:1]1[CH2:15][CH2:14][CH2:13][CH:2]1[C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].C(N(CC)CC)C.[C:23](Cl)(Cl)=[O:24].C1(C)C=CC=CC=1.[C:34]1([CH2:40][O:41][C:42]([NH:44][C@H:45]2[CH2:48][NH:47][C:46]2=[O:49])=[O:43])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.CN(C1C=CC=CN=1)C>ClCCl>[C:34]1([CH2:40][O:41][C:42]([NH:44][CH:45]2[CH2:48][N:47]([C:46]([N:1]3[CH2:15][CH2:14][CH2:13][C@H:2]3[C:3]([O:5][CH2:6][C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)=[O:4])=[O:49])[C:23]2=[O:24])=[O:43])[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1

Participants

8

Reactant 6

HCID 1140TolueneHCID 6371PhosgeneHCID 8471Triethylamine2×HCID 218852-DimethylaminopyridineHCID 99767Proline benzyl esterHCID 12834624benzyl N-[(3S)-2-oxoazetidin-3-yl]carbamate

Product 1

HCID 131714549(S)-1-[[3-[[(Phenylmethoxy)carbonyl]amino]-2-oxo-1-azetidinyl]carbonyl]-D-proline, phenylmethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-25 °C

Procedure

A solution of d,l-proline, benzyl ester (1.13 grams, 5.5 mmol) in 6 ml of dichloromethane was cooled to 0° C. and 1.2 equivalents (0.92 ml) of triethylamine (668 mg, 6.6 mmol) was added. The resulting mixture was immediately added dropwise to a solution of 20% phosgene in toluene (6 ml, 9.9 mmol) at -25° C. After stirring at -25° C. for 1 hour, the volatiles were evaporated without external heating, and the residue was redissolved in 10 ml of dichloromethane and cooled to 0° C. (S)-3-[[(Phenylmethoxy)carbonyl]amino]-2-azetidinone (1.21 grams, 5.5 mmol) and dimethylaminopyridine (67 mg, 0.55 mmol) were added to the stirring solution. Triethylamine (0.92 ml, 6.6 mmol) was added and the reaction mixture was warmed to room temperature and stirred for 24 hours. The reaction mixture was washed with water, dried over anhydrous Na2SO4, filtered and the dichloromethane removed in vacuo. The residue was purified by flash chromatography on silica gel 230-400 mesh (eluting with 40% ethyl acetate in hexane) yielding 1.2 grams of the title compound as a colorless oil.

Workup

  1. customthe volatiles were evaporated without external heating
  2. dissolutionthe residue was redissolved in 10 ml of dichloromethane
  3. additionwere added to the stirring solution
  4. temperaturethe reaction mixture was warmed to room temperature
  5. stirringstirred for 24 hours
  6. washThe reaction mixture was washed with water
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. customthe dichloromethane removed in vacuo
  10. customThe residue was purified by flash chromatography on silica gel 230-400 mesh (eluting with 40% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-7d1f728b7dc74347a8ec4713f0ef4163
Source dataset
uspto-grants-1986_03
Patent number
US04576749

Reaction notes

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