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

HRID 1365495Notes

Reaction equation

HRID 1365495 reaction equation
[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

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-f6b7a76b90804c6c90da5c48e315b9b2
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

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