Dichloromethane → 4-(2,2-Dimethylpropionyloxy)pyrazolidine-1,2-dicarboxylic acid 1-benzyl ester 2-tert-butyl ester

HRID 1581535Notes

Reaction equation

HRID 1581535 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([OH:13])[CH2:10][N:9]1[C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][C:25]([CH3:30])([CH3:29])[C:26](Cl)=[O:27].ClCCl>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([O:13][C:26](=[O:27])[C:25]([CH3:30])([CH3:29])[CH3:24])[CH2:10][N:9]1[C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 62493Pivaloyl chlorideHCID 207247531-Benzyl 2-(tert-butyl) 4-hydroxypyrazolidine-1,2-dicarboxylate

Product 1

HCID 207247514-(2,2-Dimethylpropionyloxy)pyrazolidine-1,2-dicarboxylic acid 1-benzyl ester 2-tert-butyl esterYield 98%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

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.

Workup

  1. customThe cloudy reaction mixture
  2. concentrationis then concentrated in vacuo
  3. customto afford a white residue
  4. washthe mixture washed with a 1.0 N aqueous solution of hydrochloric acid (75 mL)
  5. extractionThe aqueous layer is extracted with dichloro-methane (75 mL)
  6. washthe combined organic layers washed with a saturated aqueous solution of NaHCO3 (75 mL), water (75 mL), brine (75 mL)
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto afford the crude product
  11. customThe crude product is purified over silica(4:1 to 1:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-00de6d17a7194142aa81ad03109008a6
Source dataset
uspto-grants-2004_05
Patent number
US06730668B2

Reaction notes

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