Acetic Acid → tert-Butyl cis(+/-)-4-{[(benzyloxy)carbonyl]amino}-3-(dimethylamino)piperidine-1-carboxylate

HRID 1425308노트

반응식

HRID 1425308 반응식
C=O.[C:3](O)(=O)C.[C:7]([BH3-])#[N:8].[Na+].N[C@H:12]1[C@@H:17]([NH:18][C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])[CH2:16][CH2:15][N:14]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:13]1>O1CCCC1.CO>[CH2:22]([O:21][C:19]([NH:18][C@H:17]1[CH2:16][CH2:15][N:14]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:13][C@H:12]1[N:8]([CH3:7])[CH3:3])=[O:20])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 69440349tert-Butyl (3R,4S)-3-amino-4-{[(benzyloxy)carbonyl]amino}piperidine-1-carboxylate

생성물 1

HCID 86648775tert-Butyl cis(+/-)-4-{[(benzyloxy)carbonyl]amino}-3-(dimethylamino)piperidine-1-carboxylate수율 94%

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

실험 절차

A 37% aqueous formaldehyde solution (346 μL, 4.26 mmol), acetic acid (110 μL, 1.92 mmol) and sodium cyanoborohydride (67 mg, 1.07 mmol) were added to a mixed solution of tert-butyl cis(±)-3-amino-4-{[(benzyloxy)carbonyl]amino}piperidine-1-carboxylate obtained in Example (200a) (149 mg, 0.43 mmol) in tetrahydrofuran (2 mL) and methanol (2 mL) under ice-cooling, and the mixture was stirred at room temperature for two hours. The reaction solution was concentrated under reduced pressure, and aqueous saturated sodium bicarbonate solution was added to the residue, followed by extraction with chloroform. The resulting organic layer was dried over anhydrous sodium sulfate, and then the insoluble matter was separated by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (eluent: chloroform:methanol=10:1 v/v) to obtain 152 mg of the title compound (94%) as a colorless oily substance.

후처리

  1. temperaturecooling
  2. concentrationThe reaction solution was concentrated under reduced pressure, and aqueous saturated sodium bicarbonate solution
  3. additionwas added to the residue
  4. extractionfollowed by extraction with chloroform
  5. dry with materialThe resulting organic layer was dried over anhydrous sodium sulfate
  6. customthe insoluble matter was separated by filtration
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe resulting residue was purified by silica gel column chromatography (eluent: chloroform:methanol=10:1 v/v)

출처 및 근거

ORD 기록
ord-f1edab8d9a50492db549aa4814255088
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08927588B2

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