Propionic Acid → Ethyl (2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxylate oxalate

HRID 870505노트

반응식

HRID 870505 반응식
C(O)(=O)CC.[BH4-].[Na+].[CH2:8]([O:10][C:11]([C@@H:13]1[CH2:18][CH2:17][C:16](=[N:19][O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:15][NH:14]1)=[O:12])[CH3:9].S(=O)(=O)(O)O.O.O.[C:35]([OH:40])(=[O:39])[C:36]([OH:38])=[O:37]>C(OCC)(=O)C.C(O)C>[C:35]([OH:40])(=[O:39])[C:36]([OH:38])=[O:37].[CH2:21]([O:20][NH:19][C@H:16]1[CH2:15][NH:14][C@H:13]([C:11]([O:10][CH2:8][CH3:9])=[O:12])[CH2:18][CH2:17]1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

참가 물질

8

반응물 5

HCID 1032Propionic AcidHCID 1118Sulfuric AcidHCID 61373Oxalic acid dihydrateHCID 4311764Sodium borohydrideHCID 86675006(2S)-5-[(Phenylmethoxy)imino]-2-piperidinecarboxylic Acid Ethyl Ester

생성물 1

HCID 86675004Ethyl (2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxylate oxalate

시약·촉매·용매 2

HCID 702Ethanol용매HCID 8857Ethyl Acetate용매2회

반응 조건

온도
45 °C

실험 절차

Propanoic acid (34.9 ml, 466.2 mmol, 6 eq) was added to a suspension of sodium borohydride (5.75 g, 155.4 mmol, 2 eq) in ethyl acetate (160 ml) and held until the reaction was deemed to be complete. The resulting solution was added to a solution of (S)-5-Benzyloxyimino-piperidine-2-carboxylic acid ethyl ester in ethyl acetate (120 ml total volume) and sulfuric acid (20.7 ml, 388.5 mmol, 5 eq) at −20° C. and held until reaction was deemed to be complete. The reaction was quenched by the addition of water (240 ml), then neutralized with aqueous ammonia solution. The organic layer was washed with water and concentrated in vacuo to 80 ml. The solution was warmed to 45° C. and held at this temperature. Ethanol (80 ml, 95%) at 40° C. was added, followed by a freshly prepared solution of oxalic acid dihydrate (9.8 g, 77.7 mmol) in ethanol (40 ml). The mixture was cooled and the product was isolated by filtration. The solid was washed with an ethyl acetate/ethanol mixture, then with ethyl acetate. The solid was dried to give ethyl (2S,5R)-5-[(benzyloxy)amino]piperidine-2-carboxylate ethanedioate (1:1) as a single isomer (16.4 g, 44.5 mmol, 57.3%).

후처리

  1. customheld until reaction
  2. customThe reaction was quenched by the addition of water (240 ml)
  3. washThe organic layer was washed with water
  4. concentrationconcentrated in vacuo to 80 ml
  5. additionEthanol (80 ml, 95%) at 40° C. was added
  6. temperatureThe mixture was cooled
  7. customthe product was isolated by filtration
  8. washThe solid was washed with an ethyl acetate/ethanol mixture
  9. customThe solid was dried

출처 및 근거

ORD 기록
ord-a37f8997d02246b5971852050298a37e
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08969566B2

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