(Diethylamino)sulfur trifluoride → 1-Methylethyl 4-[({2-(fluoromethyl)-6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate

HRID 423591노트

반응식

HRID 423591 반응식
O[CH2:2][C:3]1[C:8]([O:9][CH2:10][CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][CH:20]([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[CH:7][CH:6]=[C:5]([C:23]2[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=2)[N:4]=1.CCN(S(F)(F)[F:39])CC.C([O-])(O)=O.[Na+]>C(Cl)Cl>[F:39][CH2:2][C:3]1[C:8]([O:9][CH2:10][CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][CH:20]([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[CH:7][CH:6]=[C:5]([C:23]2[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=2)[N:4]=1

참가 물질

5

반응물 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 666735831-Methylethyl 4-[({2-(hydroxymethyl)-6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate

생성물 1

HCID 249937161-Methylethyl 4-[({2-(fluoromethyl)-6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate수율 66.1%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A solution of 1-methylethyl 4-[({2-(hydroxymethyl)-6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate (131 mg, 0.28 mmol) in CH2Cl2 (5 mL) was cooled to −78° C. DAST (0.12 mL, 0.85 mmol) was added dropwise. The reaction mixture was allowed to warm to ambient temperature and stirred overnight. The mixture was poured into aqueous NaHCO3 and extracted with EtOAc (50 mL×2). The combined organic extract was washed with brine and dried over Na2SO4, filtered, and the filtrate was concentrated to a purplish-red oil. The crude material was purified by flash chromatography on a silica gel column eluted with 20% EtOAc/CH2Cl2 to give 86 mg (66%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.16 (d, 2H, J=8.6 Hz), 8.00 (d, 2H, J=8.3 Hz), 7.80-7.75 (m, 1H), 7.31 (d, 1H, J=8.8 Hz), 5.58 (d, 2H, J=47.4 Hz), 4.92 (septet, 1H, J=6.2 Hz), 4.22 (bs, 2H), 3.92 (d, 2H, J=6.1 Hz), 3.07 (s, 3H), 2.85-2.70 (m, 2H), 2.15-2.00 (m, 1H), 1.90-1.80 (m, 2H), 1.40-1.20 (m, 8H); LRMS (ESI), m/z 465 (M+H).

후처리

  1. extractionextracted with EtOAc (50 mL×2)
  2. extractionThe combined organic extract
  3. washwas washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated to a purplish-red oil
  7. customThe crude material was purified by flash chromatography on a silica gel column
  8. washeluted with 20% EtOAc/CH2Cl2

출처 및 근거

ORD 기록
ord-ba185d6d1453492e9010477a9088888f
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101634B2

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