Reaction #7751

Reaction equation

4-Hydroxypyrazolidine-1,2-dicarboxylic acid 1-benzyl ester 2-tert-butyl ester

trimethylacetyl chloride

Dichloro-methane

→

desired product

Yield 98.0%

4-(2,2-dimethylpropionyloxy)pyrazolidine-1,2-dicarboxylic acid 1-benzyl ester 2-tert-butyl ester

Yield 98.0%

Solvents

pyridine

Conditions

Workup

1. 1
   OtherThe cloudy reaction mixture
2. 2
   Concentrationis then concentrated in vacuo
3. 3
   Otherto afford a white residue
4. 4
   Washthe mixture washed with a 1.0 N aqueous solution of hydrochloric acid (75 mL)
5. 5
   ExtractionThe aqueous layer is extracted with dichloro-methane (75 mL)
6. 6
   Washthe combined organic layers washed with a saturated aqueous solution of NaHCO3 (75 mL), water (75 mL), brine (75 mL)
7. 7
   Otherdried
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated in vacuo
10. 10
    Otherto afford the crude product
11. 11
    OtherThe crude product is purified over silica (4:1 to 1:1 hexane/ethyl acetate)

Procedure

4-Hydroxypyrazolidine-1,2-dicarboxylic acid 1-benzyl ester 2-tert-butyl ester, 28, (1.42 mg, 4.40 mmol) is dissolved in pyridine (22 mL). 4-Dimethylamino-pyridine (10 mg) is added followed by trimethylacetyl chloride (1.63 mL, 13.2 mmol). The reaction is stirred at ambient temperature for 12 hours. The cloudy reaction mixture is then concentrated in vacuo to afford a white residue. Dichloro-methane (75 mL) is added to the residue and the mixture washed with a 1.0 N aqueous solution of hydrochloric acid (75 mL). The aqueous layer is extracted with dichloro-methane (75 mL), the combined organic layers washed with a saturated aqueous solution of NaHCO3 (75 mL), water (75 mL), brine (75 mL), then dried, filtered and concentrated in vacuo to afford the crude product. The crude product is purified over silica (4:1 to 1:1 hexane/ethyl acetate) to afford 1.76 g (98% yield) of the desired product as a clear, viscous oil.

Source