Sodium Hydroxide → 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(7-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid

HRID 1630320Notes

Reaction equation

HRID 1630320 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:37])=[N:14][C:15]2[N:16]([N:29]=[C:30]([C:32]([O:34]CC)=[O:33])[CH:31]=2)[C:17]=1[C:18]1[C:27]([F:28])=[CH:26][C:21]2[O:22][CH2:23][CH2:24][NH:25][C:20]=2[CH:19]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>CCO>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:37])=[N:14][C:15]2[N:16]([N:29]=[C:30]([C:32]([OH:34])=[O:33])[CH:31]=2)[C:17]=1[C:18]1[C:27]([F:28])=[CH:26][C:21]2[O:22][CH2:23][CH2:24][NH:25][C:20]=2[CH:19]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 71259455Ethyl 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(7-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate

Product 1

HCID 712592156-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(7-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acidYield 89.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of ethyl 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(7-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (130 mg, 0.253 mmol) in EtOH (4 mL) was added 1N NaOH (0.303 mL, 0.303 mmol) and the resulting mixture was stirred at room temp for 4 h. At this point LCMS indicated completion of reaction. The reaction mixture concentrated and the residue diluted with water (3 mL), acidified with 1N HCl, extracted with ethyl acetate (25 mL), washed with brine (10 mL), dried (Na2SO4), filtered and concentrated to afford 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(7-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid (110 mg, 0.226 mmol, 89% yield) as off-white solid (mixture of mono and diacid and also atrope isomers) which was used as is in the next step without further purification. LCMS (M+H)=487.3.

Workup

  1. customcompletion of reaction
  2. concentrationThe reaction mixture concentrated
  3. additionthe residue diluted with water (3 mL)
  4. extractionextracted with ethyl acetate (25 mL)
  5. washwashed with brine (10 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-610e9881c93c4342a41413306fd14993
Source dataset
uspto-grants-2014_07
Patent number
US08791108B2

Reaction notes

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