Triacetoxyborohydride → 1-Cycloheptyl-4-{[(2-fluorophenyl)(methyl)amino]methyl}-3,3-dimethylpyrrolidin-2-one

HRID 16209

Reaction equation

HRID 16209 reaction equation
[CH:1]1([N:8]2[C:12](=[O:13])[C:11]([CH3:15])([CH3:14])[CH:10]([CH:16]=O)[CH2:9]2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F:18][C:19]1[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=1[NH:21][CH3:22].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C>O1CCCC1>[CH:1]1([N:8]2[CH2:9][CH:10]([CH2:16][N:21]([C:20]3[CH:23]=[CH:24][CH:25]=[CH:26][C:19]=3[F:18])[CH3:22])[C:11]([CH3:15])([CH3:14])[C:12]2=[O:13])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 2724942TriacetoxyborohydrideHCID 27590102-Fluoro-N-methylanilineHCID 870923081-Cycloheptyl-4,4-dimethyl-5-oxo-pyrrolidine-3-carbaldehyde

Product 1

HCID 248899041-Cycloheptyl-4-{[(2-fluorophenyl)(methyl)amino]methyl}-3,3-dimethylpyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of Example 4A (30 mg, 0.12 mmoles), 2-fluoro-N-methylaniline (19 mg, 0.15 mmoles) MP-triacetoxyborohydride (137 mg, 0.3 mmoles) in tetrahydrofuran (1.25 mL) was stirred for twelve hours. The reaction was filtered and solvent evaporated in vacuo. The crude reaction mixture was purified by preparative reverse phase HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 um particle size) using a gradient of 20% to 100% acetonitrile:water (0.1% trifluoroacetic acid) over eighteen minutes at a flow rate of 40 mL/minute to provide the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 6.90-7.10 (m, 4H), 4.01-4.13 (m, 1H), 3.32 (dd, J=9.88, 7.50 Hz, 1H), 3.11-3.21 (m, 2H), 3.09 (t, J=9.36 Hz, 1H), 2.83 (s, 3H), 2.17-2.27 (m, 1H), 1.59-1.70 (m, 6H), 1.45-1.57 (m, 6H), 1.16 (s, 3H), 0.95 (s, 3H). MS (APCI+) m/z 347.2 (M+H)+.

Workup

  1. filtrationThe reaction was filtered
  2. customsolvent evaporated in vacuo
  3. customThe crude reaction mixture
  4. customwas purified by preparative reverse phase HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 um particle size)

Sources & evidence

ORD record
ord-31ee6aaf27d54276a8f6358ec7884873
Source dataset
uspto-grants-2010_06
Patent number
US07737137B2

Linked notes

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