4-Methylmorpholine → [(RS)-2-allyl-N-(benzyloxycarbonyl)prolyl]-(S)-alanine methyl ester

HRID 276757Notes

Reaction equation

HRID 276757 reaction equation
C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.[CH3:19][O:20][C:21](=[O:25])[C@H:22]([CH3:24])[NH2:23].CN(C)CCCN=C=NCC.[CH2:37]([C:40]1([C:55](O)=[O:56])[CH2:44][CH2:43][CH2:42][N:41]1[C:45]([O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:46])[CH:38]=[CH2:39]>CN(C=O)C>[CH3:19][O:20][C:21](=[O:25])[C@H:22]([CH3:24])[NH:23][C:55](=[O:56])[C:40]1([CH2:37][CH:38]=[CH2:39])[CH2:44][CH2:43][CH2:42][N:41]1[C:45]([O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:46]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2733257Alanine methyl ester hydrochlorideHCID 106848391-[(Benzyloxy)carbonyl]-2-(prop-2-en-1-yl)pyrrolidine-2-carboxylic acid

Product 1

HCID 53679594[(RS)-2-allyl-N-(benzyloxycarbonyl)prolyl]-(S)-alanine methyl esterYield 83.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HOBT (7.7 g), N-methylmorpholine (6.6 g), L-alanine methyl ester hydrochloride (4.5 g) and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide (5.7 g) was added to (RS)-2-allyl-N-(benzyloxycarbonyl)proline (6.5 g) in DMF (30 ml) and the mixture was stirred for 18 hours and then evaporated. The residue was partitioned between ether and water, filtered to remove HOBt and the organic layer separated. The organic layer was evaporated and the residue was purified by chromatography on silica using a gradient of 20% ethyl acetate in hexane increasing to 50% ethyl acetate in hexane. The appropriate fractions were combined and evaporated to dryness to give [(RS)-2-allyl-N-(benzyloxycarbonyl)prolyl]-(S)-alanine methyl ester (7 g); NMR (d6-DMSO (373K)): some doubling of peaks due to the mixture of diastereoisomers, 1.25 and 1.3 (2d, 3H), 1.75 (m, 2H), 2.2 (m,2H), 2.65 (m, 1H), 2.9 (m, 1H), 3.4 (m, 1H), 3.65 (2s, 3H), 3.7 (m, 1H), 4.3 (2q, 1H), 5.0 (m, 4H), 5.7 (m,1H), 7.3 (m, 5H), 7.4 and 7.5 (bs, 1H).

Workup

  1. customevaporated
  2. customThe residue was partitioned between ether and water
  3. filtrationfiltered
  4. customto remove HOBt
  5. customthe organic layer separated
  6. customThe organic layer was evaporated
  7. customthe residue was purified by chromatography on silica using a gradient of 20% ethyl acetate in hexane increasing to 50% ethyl acetate in hexane
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-fe5bf91af6fe487cae0c77c933fb7614
Source dataset
uspto-grants-2002_03
Patent number
US06355617B1

Reaction notes

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