Water → Tert-butyl 4-(4-nitro-2-(trifluoromethyl)phenoxy)piperidine-1-carboxylate

HRID 633409Notes

Reaction equation

HRID 633409 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12].[OH:15][CH:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1.C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C.C(Cl)Cl>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([O:15][CH:16]2[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:20][CH2:21]2)=[C:3]([C:11]([F:14])([F:13])[F:12])[CH:4]=1)([O-:10])=[O:9]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 949542-Fluoro-5-nitrobenzotrifluorideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 22181018Tert-butyl 4-(4-nitro-2-(trifluoromethyl)phenoxy)piperidine-1-carboxylateYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-fluoro-4-nitro-2-(trifluoromethyl)benzene (2.0 g, 1.0 eq, 9.6 mmol) and tert-butyl 4-hydroxypiperidine-1-carboxylate (2.1 g, 1.1 eq, 10.5 mmol) was taken in annhydrous DMF (100 mL) and stirred at room temperature. Cs2CO3 (7.2 g, 2.3 eq, 22.1 mmol) was added to the above solution and the heterogeneous mixture was heated at 100° C. overnight. The reaction mixture was diluted with CH2Cl2 (100 mL) and partioned with H2O (50 mL). The layers were separated and the aqueous layer was washed with CH2Cl2 (2×50 mL). The combined organic layers were dried over Na2SO4 and concentrated to leave a crude solid. Purification of the crude mixture by column chromatography on silica gel (ISCO System) using EtOAc/hexane (gradient system from 0:10 to 2:8) as eluent gave the product in 60% yield.

Workup

  1. temperaturethe heterogeneous mixture was heated at 100° C. overnight
  2. customThe layers were separated
  3. washthe aqueous layer was washed with CH2Cl2 (2×50 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated
  6. customto leave a crude solid
  7. customPurification of the crude mixture by column chromatography on silica gel (ISCO System)
  8. customgave the product in 60% yield

Sources & evidence

ORD record
ord-3e261ca85acd4f74a0c849e8faf8bf96
Source dataset
uspto-grants-2016_04
Patent number
US09321763B2

Reaction notes

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