Ammonium Hydroxide → 3,3-Dimethylcyclobutane-1-carboxamide

HRID 715107Notes

Reaction equation

HRID 715107 reaction equation
[CH3:1][C:2]1([CH3:9])[CH2:5][CH:4]([C:6](O)=[O:7])[CH2:3]1.C(Cl)(=O)C(Cl)=O.[NH4+:16].[OH-]>C(Cl)Cl.CN(C=O)C.C1COCC1>[CH3:1][C:2]1([CH3:9])[CH2:5][CH:4]([C:6]([NH2:16])=[O:7])[CH2:3]1

Participants

7

Reactant 3

HCID 14923Ammonium HydroxideHCID 65578Oxalyl chlorideHCID 2151063,3-Dimethylcyclobutanecarboxylic acid

Product 1

HCID 5229333,3-Dimethylcyclobutane-1-carboxamideYield 89%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Treat a solution of 3,3-dimethylcyclobutylcarboxylic acid (0.500 g, 3.90 mmol) and oxalyl chloride (0.512 mL, 5.85 mmol) in DCM (30 mL) with catalytic DMF (1 drop), stir at RT for 4 h, concentrate to dryness, add additional DCM and concentrate to dryness again. Dissolve the residue in THF (10 mL), add drop-wise to a solution of NH4OH (2 mL, 51.4 mmol) in THF (20 mL), and stir at RT overnight. Extract with EtOAc (2×), wash the combined organics with brine, dry over MgSO4 and concentrate to dryness to afford the title compound (440 mg, 89%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 7.07 (s, 1H); 6.63 (s, 1H); 2.86 (m, 1H); 1.85 (m, 2H); 1.74 (m, 2H); 1.10 (s, 3H); 1.00 (s, 3H); MS(ESI) m/z: 128.2 (M+H+).

Workup

  1. concentrationconcentrate to dryness
  2. additionadd additional DCM
  3. concentrationconcentrate to dryness again
  4. dissolutionDissolve the residue in THF (10 mL)
  5. additionadd
  6. stirringstir at RT overnight
  7. extractionExtract with EtOAc (2×)
  8. washwash the combined organics with brine
  9. dry with materialdry over MgSO4
  10. concentrationconcentrate to dryness

Sources & evidence

ORD record
ord-096c5b4a17544a54b36bfe2ecec60c0f
Source dataset
uspto-grants-2015_11
Patent number
US09187474B2

Reaction notes

Loading…