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

HRID 423591ノート

反応式

HRID 423591 の反応式
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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-ba185d6d1453492e9010477a9088888f
出典データセット
uspto-grants-2012_01
特許番号
US08101634B2

反応ノート

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