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

HRID 276757ノート

反応式

HRID 276757 の反応式
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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-fe5bf91af6fe487cae0c77c933fb7614
出典データセット
uspto-grants-2002_03
特許番号
US06355617B1

反応ノート

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