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

HRID 2115607Notes

Reaction equation

HRID 2115607 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-033f602dcfbc4242a010d9c951d02b60
Source dataset
uspto-grants-2008_10
Patent number
US07435833B2

Reaction notes

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