3,5-Dimethylisoxazole → HCID 59458920、化合物

HRID 238737

反応式

HRID 238737 の反応式
[CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[O:4][N:3]=1.[Li]CCCC.[F:13][C:14]([F:42])([F:41])[O:15][C:16]1[CH:17]=[C:18]([C:22]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([O:36][C:37]([F:40])([F:39])[F:38])[CH:31]=2)=[N:23][S:24]([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])[CH:19]=[CH:20][CH:21]=1.[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[F:40][C:37]([F:38])([F:39])[O:36][C:32]1[CH:31]=[C:30]([C:22]([C:18]2[CH:19]=[CH:20][CH:21]=[C:16]([O:15][C:14]([F:42])([F:41])[F:13])[CH:17]=2)=[N:23][S@@:24]([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])[CH:35]=[CH:34][CH:33]=1.[CH3:29][C:26]([S:24]([NH:23][C:22]([C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([O:36][C:37]([F:40])([F:38])[F:39])[CH:31]=1)([C:18]1[CH:19]=[CH:20][CH:21]=[C:16]([O:15][C:14]([F:13])([F:42])[F:41])[CH:17]=1)[CH2:7][C:5]1[O:4][N:3]=[C:2]([CH3:1])[CH:6]=1)=[O:25])([CH3:27])[CH3:28]

参加物

8

反応物 4

HCID 93123,5-DimethylisoxazoleHCID 25517Ammonium ChlorideHCID 72291066HCID 72291066、化合物HCID 178418339Butyllithium

生成物 2

HCID 59458920HCID 59458920、化合物HCID 72291098HCID 72291098、化合物

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
-78 °C

実験手順

(R)—N-(bis(3-(trifluoromethoxy)phenyl)methylene)-2-methylpropane-2-sulfinamide was prepared as described for Procedure 11. Under an Argon atmosphere, 3,5-dimethylisoxazole (0.20 mL) was stirred in anhydrous THF in an oven-dried round bottomed flask at −78° C. nBuLi (2.5 M in hexanes, 0.84 mL, 2.1 mmol) was added dropwise. The resulting yellowish solution was stirred at −78° C. for 2 h. N-(bis(3-(trifluoromethoxy)phenyl)methylene)-2-methylpropane-2-sulfinamide (0.81 g, 1.8 mmol) in THF (2 mL) was added dropwise to the above stirred solution. The reaction mixture was stirred at −78° C. for 5 h, then slowly warmed up to room temperature overnight. Saturated NH4Cl was added, followed by the addition of EtOAc. The organic layer was washed with H2O and brine, dried over Na2SO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography (silica gel, EtOAc/Hexanes=0 to 100%, came out at 100% EtOAc) to give 2-methyl-N-(2-(3-methylisoxazol-5-yl)-1,1-bis(3-(trifluoromethoxy)phenyl)ethyl)propane-2-sulfinamide as light tan viscous oil (0.14 g, yield: 13.5% with 0.55 g recovery of the starting material). LC-MS (ESI) 551.38 (M+H), retention time=3.98 min (10-90% MeOH in H2O with 0.1% TFA in a 4-min run); 1H NMR (400 MHz, CDCl3) δ ppm 7.49-7.40 (m, 2H), 7.37-7.28 (m, 1H), 7.19 (d, J=6.57 Hz, 1H), 7.05-7.14 (m, 4H), 5.70 (s, 1H), 4.61 (s, 1H), 4.14 (d, J=14.40 Hz, 1H), 3.88 (d, J=14.40 Hz, 1H), 2.26 (s, 2H), 2.13 (s, 3H), 1.26 (s, 9H).

後処理

  1. additionwas added dropwise
  2. stirringThe reaction mixture was stirred at −78° C. for 5 h
  3. temperatureslowly warmed up to room temperature overnight
  4. washThe organic layer was washed with H2O and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe residue was purified by flash chromatography (silica gel, EtOAc/Hexanes=0 to 100%

出典と根拠

ORDレコード
ord-ecca07e4699544e989e1749ec5f3c949
出典データセット
uspto-grants-2014_02
特許番号
US08642576B2

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