Toluene → (R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate

HRID 2039899노트

반응식

HRID 2039899 반응식
B.C1(C)C=CC=CC=1.[Cl:9][C:10]1[CH:11]=[C:12]([CH:28]=[C:29]([F:31])[CH:30]=1)[C:13]([C@@H:15]1[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16]1)=[O:14]>C1COCC1>[Cl:9][C:10]1[CH:11]=[C:12]([C@H:13]([OH:14])[C@@H:15]2[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:16]2)[CH:28]=[C:29]([F:31])[CH:30]=1

참가 물질

5

반응물 3

HCID 1140TolueneHCID 6331BoraneHCID 58017408(R)-tert-butyl 3-(3-chloro-5-fluorobenzoyl)piperidine-1-carboxylate

생성물 1

HCID 58017388(R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

반응 조건

온도
-15 °C

실험 절차

A mixture of 10 M H3B.S2Me in THF (47.7 mL, 0.477 mol) and 1M R-CBS-oxazaborolidine in toluene (72 mL, 0.072 mol) were dissolved in 100 mL anhydrous THF and cooled to −15° C. (R)-tert-butyl 3-(3-chloro-5-fluorobenzoyl)piperidine-1-carboxylate in 400 mL anhydrous THF was added dropwise to the above solution and stirred at −15° C. for 2 hr. The reaction was quenched with methanol (500 mL). The solvent was removed under reduced pressure and the residue was purified by column chromatography. The product was re-crystallized three times with EtOAc/Hexanes to give (R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (55 g, 0.156 mol). 1H NMR (CDCl3, 400 MHz) δ 7.10 (s, 1H), 7.04-6.90 (dd, 2H), 4.46-4.30 (d, 1H), 4.05-2.40 (m, 5H), 1.74 (s, 1H), 1.60 (s, 1H), 1.53-1.31 (m, 1H), 1.30-1.14 (m, 1H).

후처리

  1. additionwas added dropwise to the above solution
  2. customThe reaction was quenched with methanol (500 mL)
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by column chromatography
  5. customThe product was re-crystallized three times with EtOAc/Hexanes

출처 및 근거

ORD 기록
ord-2f2d8f78e32f45c988922d82b5013c91
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08580823B2

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