Potassium Hydroxide → 5-(5-Bromo-2-fluoro-phenyl)-5-difluoromethyl-2-methyl-morpholin-3-one

HRID 221740Notes

Reaction equation

HRID 221740 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:20])=[C:6]([C:8]([NH:14][C:15](=[O:19])[CH:16](Cl)[CH3:17])([CH2:12][OH:13])[CH:9]([F:11])[F:10])[CH:7]=1.[OH-].[K+]>C(#N)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:20])=[C:6]([C:8]2([CH:9]([F:11])[F:10])[NH:14][C:15](=[O:19])[CH:16]([CH3:17])[O:13][CH2:12]2)[CH:7]=1

Participants

4

Reactant 2

HCID 14797Potassium Hydroxide2×HCID 66665576N-[1-(5-Bromo-2-fluoro-phenyl)-2,2-difluoro-1-hydroxymethyl-ethyl]-2-chloropropionamide

Product 1

HCID 666659295-(5-Bromo-2-fluoro-phenyl)-5-difluoromethyl-2-methyl-morpholin-3-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of N-[1-(5-bromo-2-fluoro-phenyl)-2,2-difluoro-1-hydroxymethyl-ethyl]-2-chloro-propionamide first eluting diastereomer (442 mg, 1.180 mmol) in 4.4 mL acetonitrile was treated with potassium hydroxide (86 mg, 1.298 mmol) and stirred over night. Additional potassium hydroxide (26 mg, 0.472 mmol) was added and the reaction mixture was stirred for another night. Eventually, the reaction mixture was partitioned between 1N HCl and EtOAc. The layers were separated, washed with brine and EtOAc. The combined organic layers were dried over MgSO4.H2O and evaporated. The crude product was crystallized from TBME to give 251 mg of the title compound as white crystals.

Workup

  1. stirringthe reaction mixture was stirred for another night
  2. customEventually, the reaction mixture was partitioned between 1N HCl and EtOAc
  3. customThe layers were separated
  4. washwashed with brine and EtOAc
  5. dry with materialThe combined organic layers were dried over MgSO4.H2O
  6. customevaporated
  7. customThe crude product was crystallized from TBME

Sources & evidence

ORD record
ord-b82121dbdf734cfc997a61705d2f1a84
Source dataset
uspto-grants-2012_06
Patent number
US08207164B2

Reaction notes

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