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

HRID 1278945노트

반응식

HRID 1278945 반응식
[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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매2회HCID 1140Toluene용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-c323b2634bd44bc8811641c4b4ff446a
출처 데이터셋
uspto-grants-2002_09
특허 번호
US06444826B1

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