4-Fluorobenzyl chloride → 1-benzyl-8-(2,4-dimethoxybenzoyl)-3-(S)-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4,5]decan-2-one

HRID 552344Notes

Reaction equation

HRID 552344 reaction equation
[CH3:1][O:2][C:3]1[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[CH:22][C:4]=1[C:5]([N:7]1[CH2:21][CH2:20][C:10]2([NH:14][C:13](=[O:15])[C@H:12]([CH2:16][CH2:17][S:18][CH3:19])[NH:11]2)[CH2:9][CH2:8]1)=[O:6].[H-].[Na+].F[C:31]1[CH:38]=[CH:37][C:34]([CH2:35]Cl)=[CH:33][CH:32]=1.[NH4+].[Cl-]>CN(C=O)C>[CH2:35]([N:14]1[C:10]2([CH2:20][CH2:21][N:7]([C:5](=[O:6])[C:4]3[CH:22]=[CH:23][C:24]([O:26][CH3:27])=[CH:25][C:3]=3[O:2][CH3:1])[CH2:8][CH2:9]2)[NH:11][C@@H:12]([CH2:16][CH2:17][S:18][CH3:19])[C:13]1=[O:15])[C:34]1[CH:37]=[CH:38][CH:31]=[CH:32][CH:33]=1

Participants

6

Reactant 4

HCID 96024-Fluorobenzyl chlorideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 67165786HCID 67165786, compound

Product 1

HCID 671659491-benzyl-8-(2,4-dimethoxybenzoyl)-3-(S)-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4,5]decan-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 8-(2,4-dimethoxybenzoyl)-3-(S)-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4,5]decan-2-one (400 mg, 1.0 mmol) in 10 mL of DMF there was added sodium hydride (40 mg, 1.5 mmol) at RT and under a blanket of nitrogen. Following stirring over a period of 1 h at RT, 4-fluorobenzyl chloride (160 mg, 1.1 mmol) was slowly added dropwise and the mixture was then heated for 30 min in a microwave oven at 100° C. Following the addition of an aqueous saturated NH4Cl solution (15 mL), the mixture was extracted with ether (3×10 mL), the ethereal phase washed with aqueous saturated NaHCO3 solution (2×10 mL) and the combined organic phases were dried over Na2SO4. Following removal, by distillation, of the solvent, there was obtained the crude product as a yellow oil. Further purification was carried out by column chromatography. The product 1-benzyl-8-(2,4-dimethoxybenzoyl)-3-(S)-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4,5]decan-2-one was obtained in a yield of 296 mg (58%).

Workup

  1. temperaturethe mixture was then heated for 30 min in a microwave oven at 100° C
  2. extractionthe mixture was extracted with ether (3×10 mL)
  3. washthe ethereal phase washed with aqueous saturated NaHCO3 solution (2×10 mL)
  4. dry with materialthe combined organic phases were dried over Na2SO4
  5. customremoval
  6. distillationby distillation
  7. customof the solvent, there was obtained the crude product as a yellow oil
  8. customFurther purification

Sources & evidence

ORD record
ord-c2185cb5aa6b4d70b4930c4a17623547
Source dataset
uspto-grants-2011_05
Patent number
US07951815B2

Reaction notes

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