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Boron tribromide → (S)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-hydroxyphenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide

HRID 1365495
ノート
印刷プレビュー

反応式

HRID 1365495 の反応式
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:25][C:26](=[O:38])[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[C:29]([C:34]([F:37])([F:36])[F:35])[CH:28]=2)([C:16]2[CH:21]=[C:20]([O:22]C)[CH:19]=[C:18]([F:24])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1.B(Br)(Br)Br>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:25][C:26](=[O:38])[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[C:29]([C:34]([F:36])([F:35])[F:37])[CH:28]=2)([C:16]2[CH:21]=[C:20]([OH:22])[CH:19]=[C:18]([F:24])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

4

反応物 2

HCID 25134Boron tribromideHCID 58920898(S)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-methoxyphenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide

生成物 1

HCID 58920056(S)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-hydroxyphenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To a solution of (S)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-methoxyphenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide (696 mg, 1.27 mmol, prepared according to procedures 5, 6, 7 and 2) in CH2Cl2 at 0° C. was added BBr3 (12.7 mL, 1M, 12.7 mmol). The mixture was stirred at 0° C. for 3 hrs before it was quenched by being carefully poured into cold Na2CO3 solution. The aqueous was extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, concentrated and the crude mixture was purified by ISCO chromatography (40 g column) using hexanes/EtOAc (0-40% over 25 min) to give (S)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-hydroxyphenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide as an offwhite solid (606 mg, 90% yield). LCMS: 4.07 min [M+1] 533.30 (4 min gradient, MeOH/H2O 0.1% TFA); 1H NMR (400 MHz, CDCl3) δ ppm 3.64 (d, J=13.21 Hz, 1 H), 4.48 (d, J=12.96 Hz, 1 H), 6.21 (dt, J=10.03, 2.20 Hz, 1 H), 6.45-6.55 (m, 3 H), 6.95-7.04 (m, 3 H), 7.11 (t, J=7.46 Hz, 1 H), 7.20-7.30 (m, 3 H), 7.53 (s, 1 H), 7.70 (dd, J=8.68, 2.32 Hz, 1 H), 7.90 (ddd, J=8.50, 4.46, 2.45 Hz, 1 H), 8.03 (dd, J=6.72, 2.08 Hz, 1 H), 8.29-8.32 (m, 1 H), 9.33-9.41 (m, 1 H).

後処理

  1. customwas quenched
  2. additionby being carefully poured into cold Na2CO3 solution
  3. extractionThe aqueous was extracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customthe crude mixture was purified by ISCO chromatography (40 g column)
  8. customhexanes/EtOAc (0-40% over 25 min)

出典と根拠

ORDレコード
ord-f6b7a76b90804c6c90da5c48e315b9b2
出典データセット
uspto-grants-2011_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07888376B2

反応ノート

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