Trimethylsilyl isocyanate → (RS)-{1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidin-3-yl}-urea

HRID 859212Notes

Reaction equation

HRID 859212 reaction equation
Cl.[NH2:2][CH:3]1[CH2:7][N:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)=[CH:10][CH:9]=2)[C:5](=[O:23])[CH2:4]1.C(N(C(C)C)C(C)C)C.C[Si]([N:37]=[C:38]=[O:39])(C)C>CN(C)C=O>[F:22][C:18]1[CH:17]=[C:16]([CH:21]=[CH:20][CH:19]=1)[CH2:15][O:14][C:11]1[CH:10]=[CH:9][C:8]([N:6]2[C:5](=[O:23])[CH2:4][CH:3]([NH:2][C:38]([NH2:37])=[O:39])[CH2:7]2)=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 70696Trimethylsilyl isocyanateHCID 81531DiisopropylethylamineHCID 68614460(RS)-4-amino-1-[4-(3-fluoro-benzyloxy)-phenyl]-pyrrolidin-2-one hydrochloride

Product 1

HCID 10043062(RS)-{1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidin-3-yl}-ureaYield 60.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 250 mg (0.74 mmol) of (RS)-4-amino-1-[4-(3-fluoro-benzyloxy)-phenyl]-pyrrolidin-2-one hydrochloride [Example 1f)] in 2 ml of N,N-dimethylformamide is cooled to 0° C. and successively treated with 386 μl (2.2 mmol) of N-ethyl-diisopropylamine and 307 μl (2.2 mmol) of trimethylsilylisocyanate. The mixture is left to warm to RT and stirred for 4 hours. For the working-up, the reaction mixture is evaporated under reduced pressure. The red residue is dissolved in dichloromethane and the organic phase washed with water. After separation of the organic layer and drying over sodium sulfate, it is evaporated to give a red oil. For purification, the crude product is chromatographed on silica gel using a gradient of a 95:5- to 90:10-mixture of dichloromethane and methanol as the eluent. After the chromatography, in addition, the product is triturated in ethyl acetate and sodium hydrogencarbonate at RT. There are obtained 153 mg (60% of theory) of (RS)-{1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidin-3-yl}-urea as a white solid. MS: m/e=344 (M+H)+.

Workup

  1. waitThe mixture is left
  2. customthe reaction mixture is evaporated under reduced pressure
  3. dissolutionThe red residue is dissolved in dichloromethane
  4. washthe organic phase washed with water
  5. customAfter separation of the organic layer
  6. dry with materialdrying over sodium sulfate, it
  7. customis evaporated
  8. customto give a red oil
  9. customFor purification
  10. customthe crude product is chromatographed on silica gel using a gradient of a 95:5- to 90
  11. customAfter the chromatography, in addition, the product is triturated in ethyl acetate
  12. customat RT

Sources & evidence

ORD record
ord-43679012b520429e8928189bdb5e5b9e
Source dataset
uspto-grants-2006_12
Patent number
US07151111B2

Reaction notes

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