Water → (R)-tert-butyl 3-((R)-hydroxy(phenyl)methyl)piperidine-1-carboxylate

HRID 253544

반응식

HRID 253544 반응식
[C:1]([C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B1(C)OC(C2C=CC=CC=2)(C2C=CC=CC=2)[C@@H]2N1CCC2.[B]1OC2C(=CC=CC=2)O1.O>C1(C)C=CC=CC=1.CCOCC>[OH:8][C@@H:1]([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:10]1

참가 물질

7

반응물 4

HCID 962WaterHCID 6327445BenzcatechinboraneHCID 9838490(R)-2-Methyl-CBS-oxazaborolidineHCID 59382841tert-Butyl (3R)-3-benzoylpiperidine-1-carboxylate

생성물 1

HCID 57388686(R)-tert-butyl 3-((R)-hydroxy(phenyl)methyl)piperidine-1-carboxylate수율 43%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 3283Diethyl Ether용매

반응 조건

온도
0 °C

실험 절차

A solution of (R)-tert-butyl 3-benzoylpiperidine-1-carboxylate (10.3 g, 35.64 mmol) in anhydrous toluene (120 mL) was cooled to −78° C. and (R)-2-methyl-CBS-oxazaborolidine (1.0M in toluene, 17.8 mL, 17.8 mmol, 0.5 equiv) was added slowly. After 5 min, catecholborane (11.4 mL, 107 mmol, 3 equiv) was added slowly. The reaction mixture was then transferred into the freezer (−14° C.) and left overnight. LC-MS (16 min) showed a 9:1 ratio of the R to the S isomer. The mixture was cooled to 0° C. and water was added dropwise to quench the reaction. The reaction mixture was diluted with ether, washed with 5% aq NaOH (2×150 mL), water (150 mL), 5% aq HCl (100 mL), and brine (100 mL), and dried over Na2SO4. After concentration, the crude product was purified by flash chromatography on a 120-g silica gel column eluted with a 4-35% EtOAc in hexanes gradient. The purified product was recrystallized from an ether/hexanes mixture to afford (R)-tert-butyl 3-((R)-hydroxy(phenyl)methyl)piperidine-1-carboxylate (4.45 g, 43%) as a white solid with the ratio of R/S isomers 23.5:1. LC-MS (3 min) tR=1.70 min; LC-MS (3 min) tR=10.62 min, m/z 314 (M+Na). 1H NMR (CDCl3) δ 7.28 (m, 5H), 4.46 (d, 1H), 3.87 (d, 1H), 3.89-3.51 (br s, free exchange 1H), 3.00 (m, 2H), 2.68 (t, 1H), 2.52 (t, 1H), 1.94 (m, 1H), 1.76 (m, 1H), 1.65 (m, 1H), 1.42-1.20 (m, 10H).

후처리

  1. customwas then transferred into the freezer (−14° C.)
  2. waitleft overnight
  3. customLC-MS (16 min)
  4. customto quench
  5. customthe reaction
  6. washwashed with 5% aq NaOH (2×150 mL), water (150 mL), 5% aq HCl (100 mL), and brine (100 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationAfter concentration
  9. customthe crude product was purified by flash chromatography on a 120-g silica gel column
  10. washeluted with a 4-35% EtOAc in hexanes gradient
  11. customThe purified product was recrystallized from an ether/hexanes mixture

출처 및 근거

ORD 기록
ord-0a53375f44cd4891905d628f6a83e04b
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07872028B2

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