Acetic Acid → 2-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2-oxoacetic acid

HRID 577870Notes

Reaction equation

HRID 577870 reaction equation
[Si:1]([O:18][CH2:19][C:20]1[C:21]([N:35]2[CH2:40][C@H:39]([CH3:41])[O:38][C@H:37]([CH3:42])[CH2:36]2)=[C:22]([F:34])[C:23]([F:33])=[C:24]([C:26](=[O:32])[C:27]([O:29]CC)=[O:28])[CH:25]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[K+].C(O)(=O)C>C(O)C.O>[Si:1]([O:18][CH2:19][C:20]1[C:21]([N:35]2[CH2:36][C@H:37]([CH3:42])[O:38][C@H:39]([CH3:41])[CH2:40]2)=[C:22]([F:34])[C:23]([F:33])=[C:24]([C:26](=[O:32])[C:27]([OH:29])=[O:28])[CH:25]=1)([C:14]([CH3:16])([CH3:15])[CH3:17])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 14797Potassium Hydroxide3×HCID 86658065Ethyl 2-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2-oxoacetate2×

Product 1

HCID 866580682-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2-oxoacetic acid

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

Ethyl 2-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2-oxoacetate (Intermediate 114, 0.785 g, 3.00 mmol) was dissolved in ethanol (60 ml) and stirred at room temperature with 1 ml of 10% KOH. After 3 hours the reaction appears to have gone approximately 40-50% by LCMS. An additional 1 ml of 10% KOH was added and the reaction was stirred at room temperature for 30 minutes. The reaction has 70-80% by LCMS. An additional 1 ml of 10% KOH was added and the reaction was stirred at room temperature for 60 minutes. The reaction was made acidic with acetic acid, diluted with water and extracted three times with ethyl acetate. The organic layers were washed twice with brine, dried over MgSO4 and concentrated. The resulting sticky oil was dissolved in ethyl acetate, washed with sat. NaHCO3, dried over MgSO4 and concentrated. The resulting oil was dried under vacuum for 2 hours to give the title compound as a yellow solid.

Workup

  1. stirringthe reaction was stirred at room temperature for 60 minutes
  2. extractionextracted three times with ethyl acetate
  3. washThe organic layers were washed twice with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. dissolutionThe resulting sticky oil was dissolved in ethyl acetate
  7. washwashed with sat. NaHCO3
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customThe resulting oil was dried under vacuum for 2 hours

Sources & evidence

ORD record
ord-81b6c9f6fc5a4f93b0c138b172ee795c
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

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