Ammonium Hydroxide → 3-(1-(Trifluoromethyl)cyclopropyl)propanamide

HRID 1049284Notes

Reaction equation

HRID 1049284 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1([CH2:6][CH2:7][C:8](O)=[O:9])[CH2:5][CH2:4]1.C(Cl)(=O)C(Cl)=O.[NH4+:19].[OH-]>C(Cl)Cl.CN(C=O)C.C1COCC1.[Cl-].[Na+].O>[F:1][C:2]([F:12])([F:11])[C:3]1([CH2:6][CH2:7][C:8]([NH2:19])=[O:9])[CH2:5][CH2:4]1

Participants

8

Reactant 3

HCID 14923Ammonium HydroxideHCID 65578Oxalyl chlorideHCID 904029993-(1-(Trifluoromethyl)cyclopropyl)propanoic acid

Product 1

HCID 904035533-(1-(Trifluoromethyl)cyclopropyl)propanamideYield 90%

Reagents, catalysts & solvents 4

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

Procedure

A solution of 3-(1-(trifluoromethyl)cyclopropyl)propanoic acid (0.2 g, 1.098 mmol) and oxalyl chloride (0.144 mL, 1.647 mmol) in DCM (5 mL) and DMF (1 drop) was stirred at RT for 2 h, then concentrated to dryness. The residue was co-evaporated with DCM (1×), then dissolved in THF (5 mL), added drop-wise to a solution of NH4OH (˜15 M, 1.07 mL, ˜16 mmol) in THF (5 mL) and stirred at RT for 0.5 h. The mixture was treated with brine, extracted with EtOAc (3×) and the combined organics were dried over Na2SO4 and concentrated to dryness to afford 3-(1-(trifluoromethyl)cyclopropyl)propanamide (179 mg, 90%). 1H NMR (400 MHz, DMSO-d6): δ 7.30 (s, 1H), 6.77 (s, 1H), 2.16 (m, 2H), 1.75 (m, 2H), 0.85 (m, 2H), 0.71 (m, 2H).

Workup

  1. concentrationconcentrated to dryness
  2. dissolutiondissolved in THF (5 mL)
  3. extractionextracted with EtOAc (3×)
  4. dry with materialthe combined organics were dried over Na2SO4
  5. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-d160d002cd7f4abbac5f29def478f774
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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