Ammonium Hydroxide → 4,4-Difluorocyclohexanecarboxamide

HRID 1049324Notes

Reaction equation

HRID 1049324 reaction equation
[F:1][C:2]1([F:11])[CH2:7][CH2:6][CH:5]([C:8](O)=[O:9])[CH2:4][CH2:3]1.C(Cl)(=O)C(Cl)=O.[NH4+:18].[OH-]>C(Cl)Cl.CN(C=O)C.C1COCC1.[Cl-].[Na+].O>[F:1][C:2]1([F:11])[CH2:7][CH2:6][CH:5]([C:8]([NH2:18])=[O:9])[CH2:4][CH2:3]1

Participants

8

Reactant 3

HCID 14923Ammonium HydroxideHCID 65578Oxalyl chlorideHCID 27791364,4-Difluorocyclohexanecarboxylic acid

Product 1

HCID 469422314,4-DifluorocyclohexanecarboxamideYield 77.4%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of 4,4-difluorocyclohexanecarboxylic acid (0.217 g, 1.322 mmol) in DCM (4 mL) was treated with oxalyl chloride (0.174 mL, 1.983 mmol) followed by catalytic DMF (1 drop) and the mixture stirred at RT for 1.5 h. The mixture was concentrated to dryness, co-evaporated with DCM (1×) and the resulting residue dissolved in THF (2 mL), added to a stirring solution of NH4OH (˜14M, 2 mL, 28.0 mmol) in THF (2 mL) and stirred for 30 minutes. The mixture was diluted with brine, extracted with EtOAc (3×) and the combined organics were dried over MgSO4 and concentrated to dryness to afford 4,4-difluorocyclohexanecarboxamide (167 mg, 77%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 7.28 (s, 1H), 6.79 (s, 1H), 2.20 (m, 1H), 2.00 (m, 2H), 1.86-1.67 (m, 4H), 1.57 (m, 2H).

Workup

  1. concentrationThe mixture was concentrated to dryness, co-evaporated with DCM (1×)
  2. dissolutionthe resulting residue dissolved in THF (2 mL)
  3. stirringstirred for 30 minutes
  4. extractionextracted with EtOAc (3×)
  5. dry with materialthe combined organics were dried over MgSO4
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-e481285497f24033a19702b19b09a06e
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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