Hydrogen Bromide → 6-Bromo-7-hydroxy-4-(4-(2-pyrrolidin-1-yl-ethoxy)-benzyl)-3-(4-trifluoromethyl-phenyl)-chromen-2-one

HRID 1296698노트

반응식

HRID 1296698 반응식
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12]C)[O:8][C:7](=[O:14])[C:6]([C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1)=[C:5]2[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][N:35]2[CH2:39][CH2:38][CH2:37][CH2:36]2)=[CH:28][CH:27]=1.Br.C(=O)(O)[O-].[Na+]>C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[OH:12])[O:8][C:7](=[O:14])[C:6]([C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:22])([F:23])[F:24])=[CH:17][CH:16]=1)=[C:5]2[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][N:35]2[CH2:36][CH2:37][CH2:38][CH2:39]2)=[CH:28][CH:27]=1

참가 물질

5

반응물 3

HCID 260Hydrogen BromideHCID 516892Sodium BicarbonateHCID 589131386-Bromo-7-methoxy-4-(4-(2-pyrrolidin-1-yl-ethoxy)-benzyl)-3-(4-trifluoromethyl-phenyl)-chromen-2-one

생성물 1

HCID 114332596-Bromo-7-hydroxy-4-(4-(2-pyrrolidin-1-yl-ethoxy)-benzyl)-3-(4-trifluoromethyl-phenyl)-chromen-2-one수율 25.5%

시약·촉매·용매 1

HCID 176Acetic Acid용매

실험 절차

A solution of 6-bromo-7-methoxy-4-(4-(2-pyrrolidin-1-yl-ethoxy)-benzyl)-3-(4-trifluoromethyl-phenyl)-chromen-2-one (0.20 g, 0.3 mmol) and hydrogen bromide in acetic acid (10 mL) was heated to reflux overnight. After cooling, excess acetic acid was removed under reduced pressure. The resulting residue was dissolved in ethyl acetate and washed with saturated sodium bicarbonate, water, and saturated sodium chloride in succession; dried over magnesium sulfate; filtered; and concnetrated under reduced pressure to afford crude product. Purification using reverse-phase preparatory HPLC (20–80% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min) provided fractions that were subsequently neutralized with sodium bicarbonate and extracted using ethyl acetate. The organic fractions were combined, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to afford the title compound (>98% pure, 45.0 mg, 23%). 1H NMR (300 MHz, d6-DMSO) δ 7.78 (m, 2H), 7.69 (s, 1H), 7.55 (m, 2H), 7.08 (m, 2H), 6.88 (s, 1H), 6.83 (m, 2H), 4.04 (t, 2H), 3.94 (s, 2H), 2.92 (t, 2H), 2.67 (bm, 4H), 1.72 (bm, 4H). MS (ESI) m/z 588.3 (M+1)+, 590.3 (M+1+2)+.

후처리

  1. temperatureto reflux overnight
  2. temperatureAfter cooling
  3. customexcess acetic acid was removed under reduced pressure
  4. dissolutionThe resulting residue was dissolved in ethyl acetate
  5. washwashed with saturated sodium bicarbonate, water, and saturated sodium chloride in succession
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customto afford crude product
  9. customPurification
  10. customreverse-phase preparatory HPLC (20–80% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min)
  11. customprovided fractions that
  12. extractionextracted
  13. dry with materialdried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-d970ab7709fb4068b4a9849d0c748548
출처 데이터셋
uspto-grants-2007_07
특허 번호
US07247646B2

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