Reaction #7754

Reaction equation

sodium hydroxide

2,2-dimethyl-propionic acid 1-[2-(4-fluorophenyl)acetyl]-pyrazolidin-4-yl ester

2-methylsulfonyl-pyrimidine-4-carbonyl chloride

→

desired product

Yield 96.6%

2,2-dimethyl-propionic acid 1-[2-(4-fluorophenyl)acetyl]-2-(methylsulfanyl-pyrimidine-4-carbonyl)-pyrazolidin-4-yl ester

Yield 96.6%

Solvents

dichloromethane

dichloromethane

Conditions

Workup

1. 1
   Washwashed with water (25 mL)
2. 2
   ExtractionThe aqueous layer is back-extracted with dichloromethane (25 mL)
3. 3
   WashThe combined organic layers are washed with a saturated aqueous solution of sodium bicarbonate (25 mL) and brine (25 mL)
4. 4
   Otherdried
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated in vacuo
7. 7
   OtherThe resulting crude material is purified over silica (1:1 hexane/ethyl acetate to 100% ethyl acetate)

Procedure

To a solution of 2,2-dimethyl-propionic acid 1-[2-(4-fluorophenyl)acetyl]-pyrazolidin-4-yl ester, 32, (427 mg, 1.79 mmol) in dichloromethane (3 mL) is added 2-methylsulfonyl-pyrimidine-4-carbonyl chloride (676 mg, 3.58 mmol) followed by dropwise addition of a 1.0 N aqueous solution of sodium hydroxide (6 mL). The mixture is vigorously stirred at room temperature for 12 hours. The reaction is diluted with dichloromethane (25 mL) and washed with water (25 mL). The aqueous layer is back-extracted with dichloromethane (25 mL). The combined organic layers are washed with a saturated aqueous solution of sodium bicarbonate (25 mL) and brine (25 mL), dried, filtered and concentrated in vacuo. The resulting crude material is purified over silica (1:1 hexane/ethyl acetate to 100% ethyl acetate) to afford 464 mg (96.6% yield) of the desired product as a brown, viscous oil.

Source