Ammonium Chloride → (2S,3S)-2-(3,4-difluorophenyl)-3,5,5-trimethylmorpholin-2-ol

HRID 1399533ノート

反応式

HRID 1399533 の反応式
[CH3:1][C@H:2]1[C:7](=[O:8])[O:6][CH2:5][C:4]([CH3:10])([CH3:9])[NH:3]1.[F:11][C:12]1[CH:13]=[C:14]([Mg]Br)[CH:15]=[CH:16][C:17]=1[F:18].[NH4+].[Cl-]>C1COCC1>[F:11][C:12]1[CH:13]=[C:14]([C@:7]2([OH:8])[O:6][CH2:5][C:4]([CH3:10])([CH3:9])[NH:3][C@H:2]2[CH3:1])[CH:15]=[CH:16][C:17]=1[F:18]

参加物

5

反応物 3

HCID 25517Ammonium ChlorideHCID 46837646HCID 46837646、化合物HCID 178505835HCID 178505835、化合物

生成物 1

HCID 46837784(2S,3S)-2-(3,4-difluorophenyl)-3,5,5-trimethylmorpholin-2-ol収率 25.8%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

A solution of morpholin-2-one 15 (410 mg, 2.86 mmol) in anhydrous THF (2.9 mL, 1M) was cooled to −78° C. and treated with 3,4-difluorophenylmagnesium bromide (1.2 equiv., 3.43 mmol, 6.90 mL, 0.5 M solution in THF) under an N2 atmosphere. After stirring the reaction mixture at −78° C. under an inert atmosphere for 1.5 h, saturated aqueous solution of NH4Cl was added to the reaction vessel. The reaction mixture was allowed to warm to room temperature and extracted with ether (three times). The combined organic extracts were washed (water, brine), dried (Na2SO4) and concentrated. Purification of the residue by column chromatography on silica gel using CH2Cl2 to CH2Cl2-MeOH—NH4OH (90:9:1) as the eluent gave 190 mg (25%) of 4m as a yellow solid: [α]22D +18.2° (c 1.0, CHCl3); 1H NMR (CDCl3) δ 7.45-7.39 (m, 1H), 7.34-7.32 (m, 1H), 7.18-7.10 (m, 1H), 3.82 (d, 1H, J=11.3 Hz), 3.40 (d, 1H, J=11.3 Hz), 3.18 (q, 1H, J=6.5 Hz), 1.38 (s, 3H), 1.08 (s, 3H), 0.78 (d, 3H, J=6.5 Hz); 13C NMR (CDCl3) δ 122.40, 122.31 116.74, 116.51, 115.8, 115.6, 96.5, 69.6, 53.4, 49.8, 27.3, 22.8, 16.5; LCMS (ESI) m/z 258.6, [(M+H)+, M=C13H17F2NO2].

後処理

  1. temperatureto warm to room temperature
  2. extractionextracted with ether (three times)
  3. washThe combined organic extracts were washed (water, brine)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customPurification of the residue by column chromatography on silica gel

出典と根拠

ORDレコード
ord-3f73679c45044b2d965d68eeeebfa398
出典データセット
uspto-grants-2014_12
特許番号
US08906908B2

反応ノート

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