4-Toluenesulfonyl chloride → Tert-butyl 4-fluoro-4-((tosyloxy)methyl)piperidine-1-carboxylate

HRID 384702노트

반응식

HRID 384702 반응식
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[F:12][C:13]1([CH2:26][OH:27])[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1.C(N(CC)CC)C>CN(C1C=CN=CC=1)C.ClCCl>[F:12][C:13]1([CH2:26][O:27][S:7]([C:4]2[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=2)(=[O:9])=[O:8])[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:17][CH2:18]1

참가 물질

6

반응물 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 22248400tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate

생성물 1

HCID 59455784Tert-butyl 4-fluoro-4-((tosyloxy)methyl)piperidine-1-carboxylate수율 80.4%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

실험 절차

p-Toluenesulfonyl chloride (230 mg, 1.209 mmol) was added portionwise to tert-butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate (188 mg, 0.806 mmol), triethylamine (227 μL, 1.612 mmol), and DMAP (9.85 mg, 0.081 mmol) in dichloromethane (2015 μL) at 0° C. The solution was stirred at room temperature overnight and then partitioned between dichloromethane and water. The organic layer was washed with 0.2M HCl and then dried (MgSO4) and concentrated. The residue was dissolved in dichloromethane and loaded onto a 25+M Biotage silica column. Chromatography, eluting with a gradient of EtOAc in hexanes, gave tert-butyl 4-fluoro-4-(tosyloxymethyl)piperidine-1-carboxylate (251 mg, 0.648 mmol, 80%) as a clear semi-solid.

후처리

  1. custompartitioned between dichloromethane and water
  2. washThe organic layer was washed with 0.2M HCl
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in dichloromethane
  6. washChromatography, eluting with a gradient of EtOAc in hexanes

출처 및 근거

ORD 기록
ord-50706a37e1f74f7da28cb79ba6a8c24d
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08367658B2

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