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

HRID 534228Notes

Reaction equation

HRID 534228 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-c770f678ca3046b2b97f1a287fdc38c7
Source dataset
uspto-grants-2014_10
Patent number
US08853408B2

Reaction notes

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