Sodium Carbonate → (3S,4R)-2-(3-benzyl-4-hydroxy-chroman-7-yl)-4-trifluoromethyl-benzoic acid 2,2-dimethylpropyl ester

HRID 1278945ノート

反応式

HRID 1278945 の反応式
[CH3:1][C:2]([CH3:21])([CH3:20])[CH2:3][O:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][C:8]=1B(O)O)=[O:6].[CH2:22]([C@@H:29]1[C@@H:38]([OH:39])[C:37]2[C:32](=[CH:33][C:34](Br)=[CH:35][CH:36]=2)[O:31][CH2:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O>[CH3:1][C:2]([CH3:21])([CH3:20])[CH2:3][O:4][C:5](=[O:6])[C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][C:8]=1[C:34]1[CH:33]=[C:32]2[C:37]([C@H:38]([OH:39])[C@@H:29]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:30][O:31]2)=[CH:36][CH:35]=1

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 11278601(3S,4R)-3-benzyl-7-bromo-chroman-4-olHCID 154622682-(Neopentyloxycarbonyl)-5-(trifluoromethyl)phenylboronic acid

生成物 1

HCID 10918078(3S,4R)-2-(3-benzyl-4-hydroxy-chroman-7-yl)-4-trifluoromethyl-benzoic acid 2,2-dimethylpropyl ester収率 84%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 1140Toluene溶媒

実験手順

A bi-phasic solution of 2-(2,2-dimethyl-propoxycarbonyl)-5-trifluoromethyl-benzeneboronic acid (1.72g, 5.66mmol), (3S, 4R)-3-benzyl-7-bromo-chroman-4-ol(1.80 g, 5.63 mmol), sodium carbonate (1.82 g, 17.2 mmol), and tretrakis(triphenyl-phosphine) palladium(0) (12 mg, 0.19 mol%) in toluene (15 mL) and water (9 mL) was stirred at reflux for 100 minutes. The reaction mixture was cooled to room temperature, poured into water (40 mL) and extracted with diisopropylether (75 mL). The organic extracts were washed with brine (50 mL), treated with Darco®G-60, dried over magnesium sulfate, filtered through Celite®,and concentrated. The crude product was purified by chromatography on silica gel (ethyl acetate/hexanes 20/80) to provide (3S, 4R)-2-(3-benzyl-4-hydroxy-chroman-7-yl)-4-trifluoromethyl-benzoic acid 2,2-dimethylpropyl ester as a white foam (2.35 g, 84% yield): Rf: 0.32 (ethyl acetate/hexanes 25/75); IR 3407 (br), 2961, 1721, 1336, 1292, 1252, 1172, 1134, 1110, 1022, 848, 749 cm−1; 1H NMR (400 MHz, CDCl3) 67 7.90 (d, J=8.1 Hz, 1H), 7.66 (d, J =8.1 Hz, 1 H), 7.63 (s, 1 H), 7.19-7.37 (m, 6H), 6.88-6.93 (m, 2H), 4.53 (t, J=4.4 Hz, 1 H), 4.22 (dd, J=11.2, 2.5 Hz, 1 H), 3.99 (dd, J=11.2, 3.3 Hz, 1 H), 3.78 (s, 2H), 2.73 (dd, J=13.8, 6.3 Hz, 1 H), 2.54 (dd, J=13.6, 9.4 Hz, 1 H), 2.20-2.80 (m, 1 H), 1.81 (d, J=5.2 Hz, 1 H), 0.74 (s, 9H); 13C NMR (100 MHz, CDCl3) 67 26.64, 30.96, 34.62, 41.53, 4.76, 67.42, 75.33, 116.77, 121.07, 122.97, 124.13, 126.44, 127.50, 127.54, 128.45, 28.60, 128.92, 129.11, 130.25, 130.31, 139.08, 141.69, 142.03, 154.44, 168.14.

後処理

  1. temperatureat reflux for 100 minutes
  2. extractionextracted with diisopropylether (75 mL)
  3. washThe organic extracts were washed with brine (50 mL)
  4. additiontreated with Darco®G-60
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered through Celite®,and
  7. concentrationconcentrated
  8. customThe crude product was purified by chromatography on silica gel (ethyl acetate/hexanes 20/80)

出典と根拠

ORDレコード
ord-c323b2634bd44bc8811641c4b4ff446a
出典データセット
uspto-grants-2002_09
特許番号
US06444826B1

反応ノート

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