Sodium hydride → HCID 45111493, compound

HRID 386922Notes

Reaction equation

HRID 386922 reaction equation
[H-].[Na+].[OH:3][CH2:4][C:5]([C:8]1[CH:12]=[C:11]([NH:13][C:14](=[O:27])[C:15]([CH3:26])([S:17]([CH2:20][CH2:21][C:22]([F:25])([F:24])[F:23])(=[O:19])=[O:18])[CH3:16])[O:10][N:9]=1)([CH3:7])[CH3:6].Br[CH2:29][CH2:30][O:31][CH3:32]>C1COCC1.O>[CH3:32][O:31][CH2:30][CH2:29][O:3][CH2:4][C:5]([C:8]1[CH:12]=[C:11]([NH:13][C:14](=[O:27])[C:15]([CH3:16])([S:17]([CH2:20][CH2:21][C:22]([F:25])([F:24])[F:23])(=[O:19])=[O:18])[CH3:26])[O:10][N:9]=1)([CH3:7])[CH3:6]

Participants

6

Reactant 3

HCID 24758Sodium hydride2×HCID 809722-Bromoethyl methyl ether2×HCID 59253207HCID 59253207, compound

Product 1

HCID 45111493HCID 45111493, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of NaH (60% in mineral oil; 11.0 mg; 0.284 mmol) in anhydrous THF (2.0 mL) is added N-[3-(2-Hydroxy-1,1-dimethyl-ethyl)-isoxazol-5-yl]-2-methyl-2-(3,3,3-trifluoro-propane-1-sulfonyl)-propionamide (50.0 mg; 0.129 mmol). The reaction is stirred at room temperature for 15 minutes and then 1-bromo-2-methoxy-ethane (0.037 mL, 0.387 mmol) is added. The reaction is stirred at 50° C. for 6 h and monitored by LC MS. Additional NaH (60% in mineral oil; 0.011 g; 0.284 mmol) and 1-bromo-2-methoxy-ethane (0.037 mL; 0.387 mmol) is added and the reaction is stirred overnight at room temperature. The crude mixture is diluted with water and extracted with ethyl acetate. The combined organics are dried over sodium sulfate, filtered and concentrated under reduced pressure. The title compound is obtained after purification by prep HPLC to afford 8 mg. Yield 14%. ESI m/z 445[M+H].

Workup

  1. stirringThe reaction is stirred at 50° C. for 6 h
  2. stirringthe reaction is stirred overnight at room temperature
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combined organics are dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b017b3e402834e93972baa9f39969b94
Source dataset
uspto-grants-2013_02
Patent number
US08372874B2

Reaction notes

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