Dimethylacetamide → methyl 2-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-6-chloroisonicotinate

HRID 1691735Notes

Reaction equation

HRID 1691735 reaction equation
[C:1]([O:5][C:6](=[O:33])[N:7]([C@@H:21]([C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1)[CH3:22])[CH2:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH:10]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([CH3:4])([CH3:3])[CH3:2].[Cl:34][C:35]1[CH:36]=[C:37]([CH:42]=[C:43](Cl)[N:44]=1)[C:38]([O:40][CH3:41])=[O:39].P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC(N(C)C)=O>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O>[C:1]([O:5][C:6]([N:7]([CH2:8][CH:9]1[CH2:14][CH2:13][N:12]([C:43]2[CH:42]=[C:37]([CH:36]=[C:35]([Cl:34])[N:44]=2)[C:38]([O:40][CH3:41])=[O:39])[CH2:11][CH:10]1[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[C@@H:21]([C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1)[CH3:22])=[O:33])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 31374DimethylacetamideHCID 62657Potassium Phosphate, TribasicHCID 93237Methyl 2,6-dichloroisonicotinateHCID 59178521HCID 59178521, compound

Product 1

HCID 86638700methyl 2-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-6-chloroisonicotinateYield 47.8%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 100 mg of tert-butyl[(1R)-1-(1-naphthyl)ethyl][(3-phenylpiperidin-4-yl)methyl]carbamate, 56 mg of methyl 2,6-dichloroisonicotinate, 95 mg of potassium phosphate, 6 mg of bis(tri-tert-butylphosphine)palladium(0), and 2.0 mL of dimethylacetamide was stirred at 100° C. overnight. The reaction mixture was cooled to room temperature, and water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 66 mg of methyl 2-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-6-chloroisonicotinate as a pale yellow oily compound. ESI+: 614

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationAfter filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-3c4f94d485d6490fb0162228ec89aabd
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

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