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

HRID 130894
Notes
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Reaction equation

HRID 130894 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
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 6344
Dichloromethane
Solvent

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 in 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 in methanol)

Sources & evidence

ORD record
ord-5234fd79369649a598eebb913852c4ae
Source dataset
uspto-grants-2008_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07381719B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes