Potassium Hydroxide → N-benzyl-trans-2-methylcyclopropanecarboxamide

HRID 899444Notes

Reaction equation

HRID 899444 reaction equation
[OH-].[K+].[CH3:3]N(N=O)C(N[N+]([O-])=O)=N.[CH2:13]([NH:20][C:21](=[O:25])/[CH:22]=[CH:23]/[CH3:24])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>CC([O-])=O.CC([O-])=O.[Pd+2].CCOCC>[CH2:13]([NH:20][C:21]([C@@H:22]1[CH2:24][C@H:23]1[CH3:3])=[O:25])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 2313079N-BenzylcrotonamideHCID 135436526N-Methyl-N'-nitro-N-nitrosoguanidine

Product 1

HCID 40201681N-benzyl-trans-2-methylcyclopropanecarboxamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 3283Diethyl EtherSolvent

Procedure

In an Erlenmeyer flask containing Et2O (300 mL) and aq. 40% KOH (111 mL) with vigorous stirring was added 1-methyl-3-nitro-1-nitrosoguanidine (11.1 g, 67 mmol) portionwise over 5 min. at rt. Upon complete addition stirring was ceased and the aq. layer frozen in a −78° bath. The ether layer was decanted into an Erlenmeyer with KOH pellets. The contents allowed to stand for 5 min., decanted into a third flask with KOH pellets and then poured onto a Et2O/THF solution (200 mL/50 mL) containing (2E)-N-benzylbut-2-enamide (3.0 g, 17.1 mmol from step A). Pd(OAc)2 (180 mg, 0.9 mmol) was subsequently added and the reaction allowed to warm to rt and stir for 1 h. Nitrogen was bubbled through the reaction for 10 min. The mixture was washed with H2O (150 mL). The organic layer was isolated and subsequently dried over Na2SO4. Solvent removal and purification by flash chromatography on SiO2 (EtOAc/hexanes) gave N-benzyl-trans-2-methylcyclopropanecarboxamide: 1H NMR (400 MHz, CDCl3) δ 7.28 (m, 5H), 5.81 (br s, 1H), 4.43 (dd, J=5.6, 2.4 Hz, 2H), 1.37 (m, 1H), 1.17 (m, 1H), 1.07 (d, J=6.0 Hz, 3H), 1.04 (overlapping m, 1H), 0.56 (m, 1H).

Workup

  1. additionUpon complete addition
  2. stirringstirring
  3. temperaturethe aq. layer frozen in a −78° bath
  4. customThe ether layer was decanted into an Erlenmeyer with KOH pellets
  5. customdecanted into a third flask with KOH pellets
  6. additionpoured onto a Et2O/THF solution (200 mL/50 mL)
  7. stirringstir for 1 h
  8. customNitrogen was bubbled through the reaction for 10 min
  9. washThe mixture was washed with H2O (150 mL)
  10. customThe organic layer was isolated
  11. dry with materialsubsequently dried over Na2SO4
  12. customSolvent removal and purification by flash chromatography on SiO2 (EtOAc/hexanes)

Sources & evidence

ORD record
ord-002b5cba32574dc4b6fb561aa47abb4d
Source dataset
uspto-grants-2008_04
Patent number
US07354942B2

Reaction notes

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