Sodium Hydroxide → 2,2-Dimethyl-propionic acid 1-[2-(4-fluorophenyl)acetyl]-2-(methylsulfanyl-pyrimidine-4-carbonyl)-pyrazolidin-4-yl ester

HRID 2220946Notes

Reaction equation

HRID 2220946 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([N:11]2[CH2:15][CH:14]([O:16][C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:13][NH:12]2)=[O:10])=[CH:4][CH:3]=1.[CH3:23][S:24]([C:27]1[N:32]=[C:31]([C:33](Cl)=[O:34])[CH:30]=[CH:29][N:28]=1)(=O)=O.[OH-].[Na+]>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([N:11]2[CH2:15][CH:14]([O:16][C:17](=[O:22])[C:18]([CH3:19])([CH3:21])[CH3:20])[CH2:13][N:12]2[C:33]([C:31]2[CH:30]=[CH:29][N:28]=[C:27]([S:24][CH3:23])[N:32]=2)=[O:34])=[O:10])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 207247362,2-Dimethyl-propionic acid 1-[2-(4-fluorophenyl)acetyl]-pyrazolidin-4-yl esterHCID 219921942-Methylsulfonyl-pyrimidine-4-carbonyl chloride

Product 1

HCID 207247342,2-Dimethyl-propionic acid 1-[2-(4-fluorophenyl)acetyl]-2-(methylsulfanyl-pyrimidine-4-carbonyl)-pyrazolidin-4-yl esterYield 96.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

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.

Workup

  1. washwashed with water (25 mL)
  2. extractionThe aqueous layer is back-extracted with dichloromethane (25 mL)
  3. washThe combined organic layers are washed with a saturated aqueous solution of sodium bicarbonate (25 mL) and brine (25 mL)
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude material is purified over silica (1:1 hexane/ethyl acetate to 100% ethyl acetate)

Sources & evidence

ORD record
ord-6b7d081622c947168af378a8c75a330c
Source dataset
uspto-grants-2008_05
Patent number
US07368455B2

Reaction notes

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