Bromomethylcyclopropane → HCID 58537898, compound

HRID 1473757Notes

Reaction equation

HRID 1473757 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-6f04ebf060944755b88510b1bcea5448
Source dataset
uspto-grants-2015_04
Patent number
US09018135B2

Reaction notes

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