Sodium hydride → HCID 117870291, compound

HRID 530585Notes

Reaction equation

HRID 530585 reaction equation
Cl[CH2:2][C:3]([NH:5][CH2:6][C@@H:7]([C:9]1[CH:14]=[CH:13][C:12]([F:15])=[C:11]([C:16]([F:19])([F:18])[F:17])[CH:10]=1)[OH:8])=[O:4].[H-].[Na+]>C1COCC1>[F:15][C:12]1[CH:13]=[CH:14][C:9]([C@@H:7]2[CH2:6][NH:5][C:3](=[O:4])[CH2:2][O:8]2)=[CH:10][C:11]=1[C:16]([F:19])([F:18])[F:17]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 117870516HCID 117870516, compound

Product 1

HCID 117870291HCID 117870291, compoundYield 22.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(R)-2-Chloro-N-(2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-hydroxyethyl)acetamide (2.45 g, 8.2 mmol) was dissolved in dry THF (30 mL). Under ice bath, sodium hydride (330 mg, 60% in mineral oil, 8.2 mmol) was added. The mixture was stirred at room temperature for 1 h and then warmed to room temperature and further stirred for 2 h. TLC indicated complete consumption of the starting material. The mixture was concentrated and extracted with ethyl acetate and water. The organic layer was dried and concentrated. The oily residue was dried in vacuum (2.25 g). This material was purified through ISCO flash column chromatography (80 g silica gel, methanol in dichloromethane, 0% to 5% gradient). The desired fraction was concentrated and crystallized from ether and hexanes to give (R)-6-(4-fluoro-3-trifluoromethyl-phenyl)-morpholin-3-one as a white solid (492 mg). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.41-3.64 (m, 2H) 4.24-4.59 (m, 2H) 4.81 (dd, J=9.06, 4.53 Hz, 1H) 6.51 (br. s., 1H) 7.17-7.27 (m, 1H) 7.51-7.62 (m, 1H) 7.66 (dd, J=6.61, 2.08 Hz, 1H). The mother liquor was concentrated to give a waxy material (230 mg), which TLC indicated it was mostly desired compound.

Workup

  1. temperaturewarmed to room temperature
  2. stirringfurther stirred for 2 h
  3. customconsumption of the starting material
  4. concentrationThe mixture was concentrated
  5. extractionextracted with ethyl acetate and water
  6. customThe organic layer was dried
  7. concentrationconcentrated
  8. customThe oily residue was dried in vacuum (2.25 g)
  9. customThis material was purified through ISCO flash column chromatography (80 g silica gel, methanol in dichloromethane, 0% to 5% gradient)
  10. concentrationThe desired fraction was concentrated
  11. customcrystallized from ether and hexanes

Sources & evidence

ORD record
ord-52c6fa978f1d4cae9c763f3a85a47d7a
Source dataset
uspto-grants-2016_05
Patent number
US09353096B2

Reaction notes

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