Sodium Hydroxide → 6-(1-tert-Butoxycarbonyl-piperidin-4-ylamino)-4-trifluoromethyl-nicotinic acid methyl ester

HRID 913089Notes

Reaction equation

HRID 913089 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]1[C:9]([C:10]([F:13])([F:12])[F:11])=[CH:8][C:7](Cl)=[N:6][CH:5]=1.[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([NH2:29])[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].[OH-].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:15])[C:4]1[C:9]([C:10]([F:13])([F:12])[F:11])=[CH:8][C:7]([NH:29][CH:26]2[CH2:25][CH2:24][N:23]([C:21]([O:20][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:22])[CH2:28][CH2:27]2)=[N:6][CH:5]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 12682914-Amino-1-Boc-piperidineHCID 2775340Methyl 6-chloro-4-(trifluoromethyl)nicotinate

Product 1

HCID 673987916-(1-tert-Butoxycarbonyl-piperidin-4-ylamino)-4-trifluoromethyl-nicotinic acid methyl esterYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 6-chloro-4-trifluoromethyl-nicotinic acid methyl ester (2.00 g, 8.35 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (2.01 g, 10.02 mmol, 1.2 equiv; commercially available) in anhydrous DMF (10 mL) was heated by microwave irradiation to 110° C. for 4 h. A solution of 1 M NaOH (100 mL) was added and the reaction mixture extracted with ethyl acetate (3×100 mL). The combined organic phases were dried over MgSO4, concentrated by evaporation under reduced pressure and the crude material purified with column chromatography on silica eluting with a gradient of heptane/ethyl acetate (5:1→3:1) to yield 1.65 g (49%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 1.36-1.41 (m, 2H), 1.40 (s, 9H), 1.95-1.97 (m, 2H), 2.85-2.93 (m, 2H), 3.81 (s, 3H), 3.92-3.98 (m, 1H), 3.98-4.05 (m, 2H), 5.12 (d, J=8.1 Hz, 1H), 6.59 (s, 1H), 8.68 (s, 1H). 19F NMR (282 MHz, CDCl3): δ-62.38. MS (ISP): 404.5 [M+H]+.

Workup

  1. extractionthe reaction mixture extracted with ethyl acetate (3×100 mL)
  2. dry with materialThe combined organic phases were dried over MgSO4
  3. concentrationconcentrated by evaporation under reduced pressure
  4. customthe crude material purified with column chromatography on silica eluting with a gradient of heptane/ethyl acetate (5:1→3:1)

Sources & evidence

ORD record
ord-d007622aaa0341b1a64a6c5aa638e3c5
Source dataset
uspto-grants-2011_09
Patent number
US08026255B2

Reaction notes

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