Acetic Acid → Methyl 1-[(4-{[(tert-butoxycarbonyl)amino]methyl}piperidin-1-yl)methyl]cyclobutanecarboxylate

HRID 733092

반응식

HRID 733092 반응식
[C:1]([O:5][C:6](=[O:15])[NH:7][CH2:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].[CH:16]([C:18]1([C:22]([O:24][CH3:25])=[O:23])[CH2:21][CH2:20][CH2:19]1)=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>O1CCCC1>[C:1]([O:5][C:6]([NH:7][CH2:8][CH:9]1[CH2:10][CH2:11][N:12]([CH2:16][C:18]2([C:22]([O:24][CH3:25])=[O:23])[CH2:21][CH2:20][CH2:19]2)[CH2:13][CH2:14]1)=[O:15])([CH3:4])([CH3:2])[CH3:3]

참가 물질

7

반응물 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 723429Tert-butyl (piperidin-4-ylmethyl)carbamateHCID 5049666Sodium triacetoxyborohydrideHCID 15656335Methyl 1-formylcyclobutane-1-carboxylate

생성물 1

HCID 67233391Methyl 1-[(4-{[(tert-butoxycarbonyl)amino]methyl}piperidin-1-yl)methyl]cyclobutanecarboxylate수율 83.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
60 °C

실험 절차

To a stirred mixture of tert-butyl(piperidin-4-ylmethyl)carbamate (12.8 g, 60 mmol) and methyl 1-formylcyclobutanecarboxylate (2.13 g, 15 mmol, Davis, Charles R.; Swenson, Dale C.; Burton, Donald J., J. Org. Chem., 1993, 58, 6843) in tetrahydrofuran (50 mL) was added acetic acid (8.6 mL, 150 mmol) at ambient temperature. After 30 min, sodium triacetoxyborohydride (12.7 g, 60 mmol) was added to the mixture. Then, the mixture was heated to 60° C. for 2 h. After cooling, the reaction mixture was poured into sat. NaHCO3 aq. The aqueous layer was extracted with CH2Cl2 for 3 times. The combined organic phase were washed with brine, dried over MgSO4, filtered and concentrated. The residue was chromatographed on a column of silica gel eluting with hexane/ethyl acetate (1:1) to give 4.25 g (83%) of the title compound as white solid.

후처리

  1. temperatureAfter cooling
  2. extractionwas extracted with CH2Cl2 for 3 times
  3. washThe combined organic phase were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed on a column of silica gel eluting with hexane/ethyl acetate (1:1)

출처 및 근거

ORD 기록
ord-7d351ffb7d2645e6b188a7254df7a931
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07589109B2

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