p-Toluenesulfonic acid → 1-[[(3S)-3-(Benzoylamino)-2-oxo-1-azetidinyl]carbonyl]-L-proline

HRID 482931Notes

Reaction equation

HRID 482931 reaction equation
C1(CO[C:9]([NH:11][CH:12]2[CH2:15][N:14]([C:16]([N:18]3[CH2:32][CH2:31][CH2:30][C@H:19]3[C:20]([O:22]CC3C=CC=CC=3)=[O:21])=[O:17])[C:13]2=[O:33])=[O:10])C=CC=CC=1.[C:34]1(C)[CH:39]=[CH:38][C:37](S(O)(=O)=O)=[CH:36][CH:35]=1.C(N(C(C)C)CC)(C)C.C(Cl)(=O)C1C=CC=CC=1>CN(C)C=O.[Pd].O>[C:9]([NH:11][C@H:12]1[CH2:15][N:14]([C:16]([N:18]2[CH2:32][CH2:31][CH2:30][C@H:19]2[C:20]([OH:22])=[O:21])=[O:17])[C:13]1=[O:33])(=[O:10])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

8

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 7412Benzoyl chlorideHCID 81531DiisopropylethylamineHCID 131714549(S)-1-[[3-[[(Phenylmethoxy)carbonyl]amino]-2-oxo-1-azetidinyl]carbonyl]-D-proline, phenylmethyl ester

Product 1

HCID 135802301-[[(3S)-3-(Benzoylamino)-2-oxo-1-azetidinyl]carbonyl]-L-prolineYield 27.1%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of (S)-1-[[3-[[(phenylmethoxy)carbonyl]amino]-2-oxo-1-azetidinyl]carbonyl]-L-proline, phenylmethyl ester (0.35 g, 0.78 mmole; prepared as described in examples 22 and 23) in 4.5 ml of dimethylformamide with 0.15 g (0.8 mmole) of p-toluenesulfonic acid and 0.2 g of 10% palladium on charcoal was hydrogenated at 1 atmosphere and 25° C. for 3 hours. The solution was chilled to 0° C. and treated with 0.3 g (2.3 mmoles) of diisopropylethylamine followed by 0.16 g (1.1 mmole) of benzoyl chloride, and stirred at 5° C. for 31/2 days. Water (10 ml) was added to the dimethylformamide solution and the slurry filtered on Celite. The pH was 3.35, and this was adjusted to 2.0 with dilute hydrochloric acid. The solution was extracted with ethyl acetate, saturated with solid sodium chloride and extracted again. The organics were dried (sodium sulfate) and evaporated to a yellow oil which showed one major component by TLC (Rf=0.56) with some less polar impurities. The oil was dissolved in dichloromethane and diluted to cloud with hexane. Scratching gave 70 mg of a white solid, melting point 148°-151° C.

Workup

  1. filtrationthe slurry filtered on Celite
  2. extractionThe solution was extracted with ethyl acetate, saturated with solid sodium chloride
  3. extractionextracted again
  4. dry with materialThe organics were dried (sodium sulfate)
  5. customevaporated to a yellow oil which
  6. dissolutionThe oil was dissolved in dichloromethane
  7. additiondiluted

Sources & evidence

ORD record
ord-b19b93b305fa4819a1c7401a575fc2a9
Source dataset
uspto-grants-1986_03
Patent number
US04576749

Reaction notes

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