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

HRID 482930Notes

Reaction equation

HRID 482930 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].C1(C)C=CC=CC=1.Cl.[NH:36]1[CH2:50][CH2:49][CH2:48][C@@H:37]1[C:38]([O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:39]>ClCCl>[C:1]1([CH2:7][O:8][C:9]([NH:11][CH:12]2[CH2:15][N:14]([C:24]([N:36]3[CH2:50][CH2:49][CH2:48][C@H:37]3[C:38]([O:40][CH2:41][C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)=[O:39])=[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 12834624benzyl N-[(3S)-2-oxoazetidin-3-yl]carbamateHCID 22827650benzyl (2R)-pyrrolidine-2-carboxylate hydrochloride

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
-10 °C

Procedure

To a slurry of dried (S)-3-[[(phenylmethoxy)carbonyl]amino]-2-azetidinone (0.44 g, 2 mmoles) in 10 ml of dry dichloromethane under argon at -10° C. was added triethylamine (0.3 g, 3 mmoles) followed by 4 ml of 12.5% phosgene in toluene (5 mmoles). After stirring for 1.5 hours at -10° C., the solvent was evaporated, and the residue taken up in dichloromethane (10 ml) and chilled to -10° C. To this was added 0.48 g (2 mmoles) of D-proline, phenylmethyl ester, hydrochloride followed by 0.4 g (4 mmoles) of triethylamine. The mixture was stirred at -10° C. for 30 minutes, then quenched and washed with 10% monobasic potassium phosphate. The organics were washed with brine, dried (sodium sulfate), and chromatographed on silica (LPS-1) in 1:1 hexane:ethyl acetate. The pure product fractions (Rf=0.23 on silica, same system) were evaporated to give 0.42 g of a thick oil.

Workup

  1. customthe solvent was evaporated
  2. temperaturechilled to -10° C
  3. stirringThe mixture was stirred at -10° C. for 30 minutes
  4. customquenched
  5. washwashed with 10% monobasic potassium phosphate
  6. washThe organics were washed with brine
  7. dry with materialdried (sodium sulfate)
  8. customchromatographed on silica (LPS-1) in 1:1 hexane
  9. customThe pure product fractions (Rf=0.23 on silica, same system) were evaporated

Sources & evidence

ORD record
ord-badc90c11c3d4c68be8b80c9673f300b
Source dataset
uspto-grants-1986_03
Patent number
US04576749

Reaction notes

Loading…