Trifluoromethanesulfonic anhydride → (S)-3-(4-chloro-5-fluoroindolin-1-yl)dihydrofuran-2(3H)-one

HRID 1670584ノート

反応式

HRID 1670584 の反応式
C(N(CC)C(C)C)(C)C.O[C@@H:11]1[CH2:15][CH2:14][O:13][C:12]1=[O:16].FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[Cl:32][C:33]1[C:41]([F:42])=[CH:40][CH:39]=[C:38]2[C:34]=1[CH2:35][CH2:36][NH:37]2>C(Cl)Cl>[Cl:32][C:33]1[C:41]([F:42])=[CH:40][CH:39]=[C:38]2[C:34]=1[CH2:35][CH2:36][N:37]2[C@H:11]1[CH2:15][CH2:14][O:13][C:12]1=[O:16]

参加物

6

反応物 4

HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 71570702-Hydroxy-gamma-butyrolactone, (2R)-HCID 441823394-Chloro-5-fluoroindoline

生成物 1

HCID 59465668(S)-3-(4-chloro-5-fluoroindolin-1-yl)dihydrofuran-2(3H)-one収率 91.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
-40 °C

実験手順

Prepared using general procedure 1. Under an N2 atmosphere at −40° C., N,N-diisopropylethylamine (34.1 mL, 196 mmol) was added dropwise to a solution of (R)-dihydro-3-hydroxyfuran-2(3H)-one (10.0 g, 98 mmol) in CH2Cl2 (100 mL). Trifluoromethanesulfonic anhydride (17.3 mL, 103 mmol) was added dropwise to this solution maintaining the internal temperature of the reaction mixture below −40° C. Upon completion of addition, the mixture was stirred at −40° C. for 1 h. A solution of 4-chloro-5-fluoroindoline (27.6, 147 mmol) in CH2Cl2 (40 mL) was added dropwise to this solution maintaining the internal temperature of the reaction mixture below −40° C. The reaction was allowed to warm up to −20° C. and was kept at this temperature for 48 h. The reaction mixture was washed with saturated aqueous sodium bicarbonate (2×), brine, dried over magnesium sulfate, and concentrated. Purification via silica gel chromatography using 0-40% ethyl acetate in hexane gave (S)-3-(4-chloro-5-fluoroindolin-1-yl)-dihydrofuran-2(3H)-one as a white solid (22.9 g, 90%). 1H NMR (400 MHz, DMSO-d6) δ 7.07-7.02 (m, 1H), 6.50 (dd, J=3.6, 8.6 Hz, 1H), 4.88 (dd, J=9.0, 11.4 Hz, 1H), 4.44-4.39 (m, 1H), 4.29-4.22 (m, 1H), 3.60-3.54 (m, 1H), 3.28 (dd, J=8.6, 17.8 Hz, 1H), 3.07-2.92 (m, 2H), 2.43-2.28 (m, 2H). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=256.1; tR1.54 min.

後処理

  1. customPrepared
  2. temperaturemaintaining the internal temperature of the reaction mixture below −40° C
  3. additionUpon completion of addition
  4. temperaturemaintaining the internal temperature of the reaction mixture below −40° C
  5. temperatureto warm up to −20° C.
  6. waitwas kept at this temperature for 48 h
  7. washThe reaction mixture was washed with saturated aqueous sodium bicarbonate (2×), brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. customPurification via silica gel chromatography

出典と根拠

ORDレコード
ord-e5ffb83fdfca4be2ada2bebc96bb6836
出典データセット
uspto-grants-2011_08
特許番号
US07994174B2

反応ノート

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