Benzylamine → 3-(benzylamino)-N-methoxy-N-methylcyclobutanecarboxamide

HRID 707351Notes

Reaction equation

HRID 707351 reaction equation
[CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:9][O:10][N:11]([CH3:19])[C:12]([CH:14]1[CH2:17][C:16](=O)[CH2:15]1)=[O:13].C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>CO.C(O)(=O)C>[CH2:1]([NH:8][CH:16]1[CH2:17][CH:14]([C:12]([N:11]([O:10][CH3:9])[CH3:19])=[O:13])[CH2:15]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 86634348N-methoxy-N-methyl-3-oxocyclobutanecarboxamide

Product 1

HCID 866942083-(benzylamino)-N-methoxy-N-methylcyclobutanecarboxamideYield 75%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

Benzylamine (751 mg, 7.02 mmol), N-methoxy-N-methyl-3-oxocyclobutanecarboxamide (423 mg, 2.70 mmol), and sodium cyanoborohydride (237 mg, 3.78 mmol) were dissolved in 25 mL of anhydrous methanol. The pH of the solution was brought to 5 by addition of acetic acid, and the reaction was stirred for 24 hours at room temperature. The pH of the solution then was brought to 8 by addition of 1 M aqueous sodium bicarbonate. The solvents were removed under reduced pressure. The crude product was partitioned between ethyl acetate (80 mL) and water (25 mL). The organic layer was washed with water and brine and dried, purified using flash column chromatography with hexanes/ethyl acetate (2:1) as an eluant to give 3-(benzylamino)-N-methoxy-N-methylcyclobutanecarboxamide (498 mg, 2.00 mmol, 75% yield) as an oil.

Workup

  1. customThe solvents were removed under reduced pressure
  2. customThe crude product was partitioned between ethyl acetate (80 mL) and water (25 mL)
  3. washThe organic layer was washed with water and brine
  4. customdried
  5. custompurified

Sources & evidence

ORD record
ord-20baeb9cd419453cb23e8b67a964c87a
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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