Boron tribromide → HCID 118207396, compound

HRID 1507194Notes

Reaction equation

HRID 1507194 reaction equation
[F:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][N:7]2[CH2:11][CH2:10][CH:9]([N:12]3[CH2:17][CH2:16][CH:15]([C:18]4[CH:23]=[CH:22][C:21]([O:24]C)=[CH:20][CH:19]=4)[CH2:14][CH2:13]3)[C:8]2=[O:26])=[CH:4][CH:3]=1.B(Br)(Br)Br>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[CH2:11][CH2:10][CH:9]([N:12]3[CH2:17][CH2:16][CH:15]([C:18]4[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=4)[CH2:14][CH2:13]3)[C:8]2=[O:26])=[CH:27][CH:28]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 118207303HCID 118207303, compound

Product 1

HCID 118207396HCID 118207396, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-(4-fluorobenzyl)-3-(4-(4-methoxyphenyl)piperidin-1-yl)pyrrolidin-2-one (AJ) (3 g, 7.9 mmol) in dry dichloromethane (100 mL) under a N2 atmosphere at −78° C. was added 1 M boron tribromide in dichloromethane (39 mL, 39 mmol) and the resulting mixture was allowed to warm up to room temperature over 3 h, with stirring. The reaction was quenched with water (30 mL) and the organic layer was separated, washed with water and brine, and concentrated. The crude product was purified by flash chromatography on silica gel using 15% EtOAc in petroleum ether to yield racemic 1-(4-fluorobenzyl)-3-(4-(4-hydroxyphenyl)piperidin-1-yl)pyrrolidin-2-one (2.1 g, 73%); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.49-1.74 (m, 4H) 1.90-2.11 (m, 2H) 2.24-2.42 (m, 2H) 2.65-2.80 (m, 2H) 2.99-3.23 (m, 3H) 3.40-3.54 (m, 1H) 4.27-4.46 (m, 2H) 6.61-6.70 (m, 2H) 6.95-7.04 (m, 2H) 7.17-7.31 (m, 4H) 9.10-9.16 (m, 1H). LCMS: R.T. 0.880 min. LCMS (ES-API), 369.2 m/z (M+H). A portion of the racemate (40 mg) was separated via SFC on a Chiralpak-IA 250 mm×4.6 mm, 5 microm column eluting with 35% solvent B, where solvent A=CO2 and solvent B=0.3% DEA in methanol at a total flow of 3 mL/min. Peak 1 showed a RT of 4.35 min and Peak 2 showed a RT of 6.29 min.

Workup

  1. customThe reaction was quenched with water (30 mL)
  2. customthe organic layer was separated
  3. washwashed with water and brine
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography on silica gel using 15% EtOAc in petroleum ether

Sources & evidence

ORD record
ord-f6e5a203ba4145108c57cee549c3a682
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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