Bromomethylcyclopropane → HCID 58537898, compound

HRID 2176826Notes

Reaction equation

HRID 2176826 reaction equation
[CH2:1]([O:8][C:9]1[C:13]2([CH2:18][CH2:17][N:16]([O:19][CH3:20])[CH2:15][CH2:14]2)[NH:12][C:11](=[O:21])[C:10]=1[C:22]1[C:27]([CH3:28])=[CH:26][C:25]([CH3:29])=[CH:24][C:23]=1[CH3:30])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:32][CH:33]1[CH2:35][CH2:34]1.CC(C)([O-])C.[K+]>O1CCOCC1>[CH2:1]([O:8][C:9]1[C:13]2([CH2:14][CH2:15][N:16]([O:19][CH3:20])[CH2:17][CH2:18]2)[N:12]([CH2:32][CH:33]2[CH2:35][CH2:34]2)[C:11](=[O:21])[C:10]=1[C:22]1[C:23]([CH3:30])=[CH:24][C:25]([CH3:29])=[CH:26][C:27]=1[CH3:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81503BromomethylcyclopropaneHCID 23665647Potassium tert-butoxideHCID 58537922HCID 58537922, compound

Product 1

HCID 58537898HCID 58537898, compoundYield 30.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-benzyloxy-8-methoxy-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-2-one (compound P3.4) (1.0 g, 2.46 mmol) in dioxane (40 ml) was added bromomethyl-cyclopropane (1.257 ml, 1.78 g, 13.16 mmol) and potassium tert-butoxide (1.50 g, 13.37 mmol). The reaction mixture was stirred at 100° C. for 5 days, then poured on water and extracted with ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate and concentrated. The residue was suspended in ethyl acetate/heptane 1:5, stirred overnight, filtered and dried to afford a first crop of product as a white solid (350 mg). The mother liquor was concentrated, and the residue purified by chromatography on silica gel (dichloromethane/acetone 10:1) to further deliver 205 mg of product. Yield: 555 mg of 4-benzyloxy-1-cyclopropylmethyl-8-methoxy-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-2-one (compound P3.8) as a solid, mp 119-121° C.

Workup

  1. additionpoured on water
  2. extractionextracted with ethyl acetate
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. stirringstirred overnight
  7. filtrationfiltered
  8. customdried

Sources & evidence

ORD record
ord-489f0f19440f46da97d4a542670657c2
Source dataset
uspto-grants-2015_06
Patent number
US09067892B2

Reaction notes

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