Lithium borohydride → HCID 57545941、化合物

HRID 913923ノート

反応式

HRID 913923 の反応式
[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([O:16][CH2:17][C:18]2([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[C:12](OC)=[O:13])[C:8]2[C:4](=[CH:5][N:6]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:45])([CH3:44])[CH3:43])[N:7]=2)[CH:3]=1.[BH4-].[Li+]>O1CCCC1.CO>[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([O:16][CH2:17][C:18]2([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH2:12][OH:13])[C:8]2[C:4](=[CH:5][N:6]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:45])([CH3:43])[CH3:44])[N:7]=2)[CH:3]=1

参加物

5

反応物 2

HCID 4148881Lithium borohydrideHCID 57546118HCID 57546118、化合物

生成物 1

HCID 57545941HCID 57545941、化合物

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of tert-butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-methoxy-2-oxoethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (850 mg, 1.28 mmol) in tetrahydrofuran (7.4 mL) and methanol (0.37 mL) at 0° C. was added lithium borohydride (55.9 mg, 2.57 mmol). The ice bath was removed and stirring continued for 30 min. The reaction was diluted with diethyl ether and quenched by addition of saturated ammonium chloride. The ethereal was washed with water, then brine, dried over magnesium sulfate, and concentrated. Column chromatography (25%→50% ethyl acetate/n-hexane) gave 794 mg (98%) as a foam solid. 1H-NMR (CDCl3, 500 MHz) δ 8.01 (s, 1H), 7.52 (d, J=1.5 Hz, 1H), 7.33 (dd, J=8.6, 5.2 Hz, 2H), 7.05 (dd, J=8.6, 8.5 Hz, 2H), 6.75 (s, 1H), 5.65 (d, J=10.7 Hz, 1H), 5.62 (d, J=10.7 Hz, 1H), 4.95 (dd, J=7.0, 3.4 Hz, 1H), 3.55-3.85 (m, 6H), 3.52 (d, J=8.9 Hz, 1H), 3.41 (d, J=8.9 Hz, 1H), 3.06 (m, 2H), 2.10-2.35 (m, 3H), 1.88 (m, 2H), 1.43 (s, 9H), 0.90 (t, J=8.2 Hz, 2H), −0.06 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 161.5 (d, J=246 Hz), 155.0, 145.7, 138.6, 130.2, 128.8 (d, J=7.7 Hz), 128.1, 124.2, 122.8, 122.5, 118.5, 115.4 (d, J=21 Hz), 81.9, 79.5, 79.1, 78.6, 67.7, 66.2, 41.5, 40.0, 32.3, 32.2, 28.6, 17.9, −1.4. Mass spec.: 634.38 (MH)+.

後処理

  1. customThe ice bath was removed
  2. additionThe reaction was diluted with diethyl ether
  3. customquenched by addition of saturated ammonium chloride
  4. washThe ethereal was washed with water
  5. dry with materialbrine, dried over magnesium sulfate
  6. concentrationconcentrated
  7. customColumn chromatography (25%→50% ethyl acetate/n-hexane) gave 794 mg (98%) as a foam solid

出典と根拠

ORDレコード
ord-715618c7a1eb4d3881b86f8684c465b9
出典データセット
uspto-grants-2011_09
特許番号
US08026257B2

反応ノート

読み込み中…