Diisopropylethylamine → tert-Butyl [(3S,5R)-1-(3-nitropyridin-4-yl)-5-(trifluoromethyl)piperidin-3-yl]carbamate

HRID 924455Notes

Reaction equation

HRID 924455 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[F:11][C:12]([F:28])([F:27])[C@H:13]1[CH2:18][NH:17][CH2:16][C@@H:15]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:14]1.CCN(C(C)C)C(C)C>C(O)(C)C>[N+:8]([C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:2]=1[N:17]1[CH2:18][C@H:13]([C:12]([F:28])([F:27])[F:11])[CH2:14][C@H:15]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:24])([CH3:23])[CH3:25])[CH2:16]1)([O-:10])=[O:9]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27357814-Chloro-3-nitropyridineHCID 73977851tert-butyl N-[(3S,5R)-5-(trifluoromethyl)piperidin-3-yl]carbamate

Product 1

HCID 86726899tert-Butyl [(3S,5R)-1-(3-nitropyridin-4-yl)-5-(trifluoromethyl)piperidin-3-yl]carbamateYield 85.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-chloro-3-nitropyridine (580 mg, 3.6 mmol), tert-butyl [(3S,5R)-5-(trifluoromethyl)piperidin-3-yl]carbamate (800 mg, 3 mmol), isopropyl alcohol (5.0 mL) and DIPEA (1.0 mL, 6.0 mmol) was stirred at 80° C. overnight. The reaction mixture was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel using CombiFlash® apparatus eluting with 50-100% EtOAc/hexanes. The purification gave 1.0 g (80% yield) of the sub-title compound as a yellow solid. LCMS calc. for C16H22F3N4O4(M+H)+: m/z=: 391.2. found: 391.1.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue was purified by column chromatography on silica gel using CombiFlash® apparatus
  3. washeluting with 50-100% EtOAc/hexanes
  4. customThe purification

Sources & evidence

ORD record
ord-f8ff80d468474d37a0d96b601fbbbe85
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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