Boron tribromide → 3-cyclopentyl-2-(3-fluoro-4-hydroxy-phenyl)-N-thiazol-2-yl-propionamide

HRID 398641Notes

Reaction equation

HRID 398641 reaction equation
[CH:1]1([CH2:6][CH:7]([C:16]2[CH:21]=[CH:20][C:19]([O:22]C)=[C:18]([F:24])[CH:17]=2)[C:8]([NH:10][C:11]2[S:12][CH:13]=[CH:14][N:15]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.B(Br)(Br)Br>C(Cl)Cl>[CH:1]1([CH2:6][CH:7]([C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([F:24])[CH:17]=2)[C:8]([NH:10][C:11]2[S:12][CH:13]=[CH:14][N:15]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 223151793-cyclopentyl-2-(3-fluoro-4-methoxy-phenyl)-N-thiazol-2-yl-propionamide

Product 1

HCID 223152383-cyclopentyl-2-(3-fluoro-4-hydroxy-phenyl)-N-thiazol-2-yl-propionamideYield 73.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-(3-fluoro-4-methoxy-phenyl)-N-thiazol-2-yl-propionamide (prepared as in Example 118, 305.4 mg, 0.87 mmol) in methylene chloride (8.7 mL) at 25° C. was treated with a 1.0M solution of boron tribromide in methylene chloride (8.75 mL, 8.75 mmol). This solution was stirred at 25° C. for 5 h. At this time, the reaction was cooled to 0° C. and quenched by the dropwise addition of a dilute aqueous ammonium hydroxide solution. The resulting solution was stirred at 0° C. for 15 min. This mixture was then poured into water (50 mL) and extracted with ethyl acetate (3×30 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 50/50 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3-fluoro-4-hydroxy-phenyl)-N-thiazol-2-yl-propionamide (212.7 mg, 72.5%) as a white solid: mp 199-201° C.: EI-HRMS m/e calcd for C17H19FN2O2S (M+) 334.1151 found 334.1152.

Workup

  1. temperatureAt this time, the reaction was cooled to 0° C.
  2. customquenched by the dropwise addition of a dilute aqueous ammonium hydroxide solution
  3. stirringThe resulting solution was stirred at 0° C. for 15 min
  4. additionThis mixture was then poured into water (50 mL)
  5. extractionextracted with ethyl acetate (3×30 mL)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5805d94ed3eb40d29a7e8b2f331982e3
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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