Methanol → 1-[4-(Cyclopropyl-hydroxy-methyl)-3-fluoro-phenyl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one

HRID 2383893Notes

Reaction equation

HRID 2383893 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[F:6][C:7]1[CH:14]=[C:13]([N:15]2[CH2:19][CH2:18][N:17]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][C:25]=3[CH3:26])[C:16]2=[O:27])[CH:12]=[CH:11][C:8]=1[CH:9]=[O:10].CO>C1COCC1.C(Cl)(Cl)Cl>[CH:1]1([CH:9]([OH:10])[C:8]2[CH:11]=[CH:12][C:13]([N:15]3[CH2:19][CH2:18][N:17]([C:20]4[CH:21]=[N:22][CH:23]=[CH:24][C:25]=4[CH3:26])[C:16]3=[O:27])=[CH:14][C:7]=2[F:6])[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 887MethanolHCID 596361642-Fluoro-4-[3-(4-methyl-pyridin-3-yl)-2-oxo-imidazolidin-1-yl]-benzaldehydeHCID 178418630HCID 178418630, compound

Product 1

HCID 596361411-[4-(Cyclopropyl-hydroxy-methyl)-3-fluoro-phenyl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-oneYield 99.41%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A 0.5M solution of cyclopropyl magnesium bromide in THF (2.4 mL, 1.170 mmol) was added dropwise to 2-fluoro-4-[3-(4-methyl-pyridin-3-yl)-2-oxo-imidazolidin-1-yl]-benzaldehyde (I-121a: 175 mg, 0.585 mmol) in dry THF (10 mL) at 0° C. under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 3 hours. The reaction was monitored by TLC (5% MeOH in CHCl3). The reaction mixture was quenched with aqueous NH4Cl solution and the THF layer was concentrated. The aqueous layer was extracted with ethylacetate. The organic layer was dried over Na2SO4 and concentrated to afford the crude product. Purification by column chromatography on silica gel (3% MeOH in CHCl3), followed by hexane wash, afforded 200 mg of the product (99.41% yield).

Workup

  1. customThe reaction mixture was quenched with aqueous NH4Cl solution
  2. concentrationthe THF layer was concentrated
  3. extractionThe aqueous layer was extracted with ethylacetate
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. customto afford the crude product
  7. customPurification by column chromatography on silica gel (3% MeOH in CHCl3)
  8. washwash

Sources & evidence

ORD record
ord-dc741ca648e14b3fba759eff055bf800
Source dataset
uspto-grants-2012_09
Patent number
US08263635B2

Reaction notes

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