Acetic Acid → (+/-)-4-[5-(3-Phenyl-pyrolidin-1-ylmethyl)-pyridin-2-yloxy]-benzamide

HRID 228346Notes

Reaction equation

HRID 228346 reaction equation
[CH:1]([C:3]1[CH:4]=[CH:5][C:6]([O:9][C:10]2[CH:18]=[CH:17][C:13]([C:14]([NH2:16])=[O:15])=[CH:12][CH:11]=2)=[N:7][CH:8]=1)=O.[C:19]1([CH:25]2[CH2:29][CH2:28][NH:27][CH2:26]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CC(O)=O>C(Cl)Cl>[C:19]1([CH:25]2[CH2:29][CH2:28][N:27]([CH2:1][C:3]3[CH:4]=[CH:5][C:6]([O:9][C:10]4[CH:18]=[CH:17][C:13]([C:14]([NH2:16])=[O:15])=[CH:12][CH:11]=4)=[N:7][CH:8]=3)[CH2:26]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 31467433-PhenylpyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 597300034-(5-Formyl-pyridin-2-yloxy)-benzamide

Product 1

HCID 68748091(+/-)-4-[5-(3-Phenyl-pyrolidin-1-ylmethyl)-pyridin-2-yloxy]-benzamideYield 36.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Combine 4-(5-formyl-pyridin-2-yloxy)-benzamide (100 mg, 0.413 mmol), (±)-3-phenyl-pyrrolidine (78 mg, 0.318 mmol), sodium triacetoxy-borohydride (101 mg, 0.477 mmol), AcOH (0.018 mL, 0.318 mmol) in CH2Cl2 (5 mL). Stir at rt overnight. Pour the reaction mixture onto an SCX column, eluting with ammonia (2M methanol) followed by chromatography [CH2Cl2:ammonia (2.0 M in methanol) 20:1] to provide the title compound (43 mg, 36%). Mass spectrum (ion spray): m/z=373.9 (M+1); 1H NMR (DMSO-d6): 8.09 (d, J=1.9 Hz, 1H), 7.93 (bs, 1H), 7.89 (d, J=8.6 Hz, 2H), 7.82 (dd, J=2.2 Hz, 8.6 Hz, 1H), 7.30 (bs, 1H), 7.27-7.24 (m, 4H), 7.17-7.12 (m, 3H), 7.03 (d, J=8.3 Hz, 1H), 3.61 (dd, J=13.1 Hz, 19.5 Hz, 2H), 3.33-3.24 (m, 1H), 2.88 (t, J=8.3 Hz, 1H), 2.66 (t, J=7.0 Hz, 2H), 2.42 (t, J=8.3 Hz, 1H), 2.28-2.18 (m, 1H), 1.79-1.70 (m, 1H).

Workup

  1. additionPour the reaction mixture onto an SCX column
  2. washeluting with ammonia (2M methanol)

Sources & evidence

ORD record
ord-2baacd61c3b64956b821460dcfe6c153
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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