Methyl chloroformate → 1-tert-Butyl 4-methyl 4-(hydroxymethyl)piperidine-1,4-dicarboxylate

HRID 655966노트

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HRID 655966 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:17]([O:19][CH3:20])=[O:18])([C:14](O)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.ClC(OC)=O.[BH4-].[Na+]>C1COCC1.CO>[OH:15][CH2:14][C:11]1([C:17]([O:19][CH3:20])=[O:18])[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[CH2:13][CH2:12]1

참가 물질

7

반응물 4

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 4311764Sodium borohydrideHCID 579202821-((Tert-butoxy)carbonyl)-4-(methoxycarbonyl)piperidine-4-carboxylic acid

생성물 1

HCID 579202781-tert-Butyl 4-methyl 4-(hydroxymethyl)piperidine-1,4-dicarboxylate수율 46%

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

To a solution of 1-(tert-butoxycarbonyl)-4-(methoxycarbonyl)piperidine-4-carboxylic acid (6 g, 21 mmol) and DIEA (7.3 mL, 42 mmol, 2.0 equiv.) in THF (60 mL) was added methyl chloroformate (1.94 mL, 25 mmol, 1.2 equiv.) at 0° C. The mixture was stirred at 0° C. until the reaction was complete. NaBH4 (3.16 g, 84 mmol, 4.0 equiv.) was added at 0° C. MeOH (10 mL) was then added. The mixture was stirred at 0° C. for 90 min. The reaction mixture was then quenched by saturated NaHCO3 and concentrated to dryness. The residue was dissolved in ethyl acetate, washed with saturated NaHCO3, water and brine, dried over Na2SO4, and concentrated. The resulting residue was purified by column chromatography to give 1-tert-butyl 4-methyl 4-(hydroxymethyl)piperidine-1,4-dicarboxylate (2.6 g, 46%). LRMS (M-Boc+H+) m/z 174.1.

후처리

  1. stirringThe mixture was stirred at 0° C. for 90 min
  2. customThe reaction mixture was then quenched by saturated NaHCO3
  3. concentrationconcentrated to dryness
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with saturated NaHCO3, water and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe resulting residue was purified by column chromatography

출처 및 근거

ORD 기록
ord-c02f69a24512453783efbfc8e04f8067
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08071625B2

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