Sodium triacetoxyborohydride → Methyl 2-chloro-4-((4-((2,2,2-trifluoro-N-((1R,2S)-2-phenylcyclopropyl)acetamido)methyl)piperidin-1-yl)methyl)benzoate

HRID 529376Notes

Reaction equation

HRID 529376 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]([N:5]([C@@H:13]1[CH2:15][C@H:14]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:6][CH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)=[O:4].[Cl:24][C:25]1[CH:34]=[C:33]([CH:35]=O)[CH:32]=[CH:31][C:26]=1[C:27]([O:29][CH3:30])=[O:28].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:24][C:25]1[CH:34]=[C:33]([CH2:35][N:10]2[CH2:9][CH2:8][CH:7]([CH2:6][N:5]([C@@H:13]3[CH2:15][C@H:14]3[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:3](=[O:4])[C:2]([F:1])([F:22])[F:23])[CH2:12][CH2:11]2)[CH:32]=[CH:31][C:26]=1[C:27]([O:29][CH3:30])=[O:28]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 57461225Methyl 2-chloro-4-formylbenzoateHCID 867082342,2,2-trifluoro-N-((1R,2S)-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide

Product 1

HCID 86708271Methyl 2-chloro-4-((4-((2,2,2-trifluoro-N-((1R,2S)-2-phenylcyclopropyl)acetamido)methyl)piperidin-1-yl)methyl)benzoateYield 22.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 2,2,2-trifluoro-N-((1R,2S)-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide (100 mg, 0.306 mmol) in 1,2-dichloroethane (DCE) (2 mL) were added methyl 2-chloro-4-formylbenzoate (73.0 mg, 0.368 mmol) and sodium triacetoxyborohydride (104 mg, 0.490 mmol), and the reaction mixture was stirred at room temperature for 18 h. The mixture was quenched with water (4 mL) and extracted with DCM (3×). The extract was dried (Na2SO4) and concentrated. The residue was purified using column chromatography (silica gel, 0 to 100% EtOAc/hexanes, then 0 to 10% MeOH/EtOAc) to give 35 mg of product as off-white solid. MS: (M+H)+=509.2. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.28-1.78 (m, 7H), 1.81-1.94 (m, 1H), 2.09-2.21 (m, 2H), 2.39-2.54 (m, 1H), 2.89-3.01 (m, 2H), 3.10-3.22 (m, 1H), 3.41-3.67 (m, 4H), 3.90-3.95 (m, 3H), 7.12-7.42 (m, 6H), 7.53 (s, 1H), 7.81 (d, J=8.08 Hz, 1H).

Workup

  1. customThe mixture was quenched with water (4 mL)
  2. extractionextracted with DCM (3×)
  3. dry with materialThe extract was dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified

Sources & evidence

ORD record
ord-1edaebd9b4684097a634daebd7f6eda8
Source dataset
uspto-grants-2016_05
Patent number
US09346840B2

Reaction notes

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