Triethylamine → N-(2-{[(3R)-1-(5-Hydroxy-5-pyridin-3-ylbicyclo[2.2.2]oct-2-yl)pyrrolidin-3-yl]amino}-2-oxoethyl)-3-(trifluoromethyl)benzamide

HRID 1025794Notes

Reaction equation

HRID 1025794 reaction equation
Cl.[O:2]=[C:3]([NH:18][C@@H:19]1[CH2:23][CH2:22][NH:21][CH2:20]1)[CH2:4][NH:5][C:6](=[O:17])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=1.[OH:24][C:25]1([C:34]2[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=2)[CH2:30][CH:29]2[CH2:31][CH2:32][CH:26]1[CH2:27][C:28]2=O.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[OH:24][C:25]1([C:34]2[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=2)[CH2:30][CH:29]2[CH2:31][CH2:32][CH:26]1[CH2:27][CH:28]2[N:21]1[CH2:22][CH2:23][C@@H:19]([NH:18][C:3](=[O:2])[CH2:4][NH:5][C:6](=[O:17])[C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:15])([F:16])[F:14])[CH:8]=2)[CH2:20]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 595560585-Hydroxy-5-pyridin-3-ylbicyclo[2.2.2]octan-2-oneHCID 66787629N-{2-Oxo-2-[(3R)-pyrrolidin-3-ylamino]ethyl}-3-(trifluoromethyl)benzamide hydrochloride

Product 1

HCID 59556078N-(2-{[(3R)-1-(5-Hydroxy-5-pyridin-3-ylbicyclo[2.2.2]oct-2-yl)pyrrolidin-3-yl]amino}-2-oxoethyl)-3-(trifluoromethyl)benzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-{2-Oxo-2-[(3R)-pyrrolidin-3-ylamino]ethyl}-3-(trifluoromethyl)benzamide hydrochloride (100 mg, 0.284 mmol) and 5-hydroxy-5-pyridin-3-ylbicyclo[2.2.2]octan-2-one (62.0 mg, 0.284 mmol) were dissolved in dry THF (10 mL). Triethylamine (80 uL, 0.57 mmol) and sodium triacetoxyborohydride (120 mg, 0.57 mmol) were added and the mixture was stirred at room temperature overnight. TLC indicated conversion to desired products in about a 1:1 ratio of isomers. Adsorbed reaction mixture onto silica gel and chromatographed eluting with dichloromethane to 10% methanol/dichloromethane/0.5% ammonium hydroxide. Fractions were combined to give pure higher Rf isomer and pure lower Rf isomer: Higher Rf product: LC/MS (positive ion) m/z=517.1 (M+H)+; Lower Rf product: LC/MS (positive ion) m/z=517.2 (M+H)+.

Workup

  1. customAdsorbed reaction mixture onto silica gel
  2. customchromatographed
  3. washeluting with dichloromethane to 10% methanol/dichloromethane/0.5% ammonium hydroxide
  4. customto give pure higher Rf isomer and pure lower Rf isomer

Sources & evidence

ORD record
ord-10f73693b98048a8bb11f1ee8a079db0
Source dataset
uspto-grants-2014_05
Patent number
US08729063B2

Reaction notes

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