Sodium hydride → [(S)-2-(7,8-Dihydro-[1,4]dioxino[2,3-g]indazol-1-yl)-1-methylethyl]-carbamic acid benzyl ester

HRID 31367Notes

Reaction equation

HRID 31367 reaction equation
[CH2:1]([O:8][C:9](=[O:28])[NH:10][C@@H:11]([CH3:27])[CH2:12][N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([O:23][CH2:24][CH2:25][OH:26])[C:20]=2Br)[CH:15]=[N:14]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH2:1]([O:8][C:9](=[O:28])[NH:10][C@@H:11]([CH3:27])[CH2:12][N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]3[O:23][CH2:24][CH2:25][O:26][C:20]3=2)[CH:15]=[N:14]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 69254543HCID 69254543, compound

Product 1

HCID 69253919[(S)-2-(7,8-Dihydro-[1,4]dioxino[2,3-g]indazol-1-yl)-1-methylethyl]-carbamic acid benzyl esterYield 19.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of the alcohol from Step C (0.36 g, 0.79 mmol) in anhydrous N,N-dimethylformamide (10 mL) was added sodium hydride (60% dispersion in mineral oil, 0.064 mg, 1.59 mmol) and cuprous iodide (0.015 g, 0.79 mmol) under a nitrogen atmosphere with stirring. After 30 min the suspension was heated at 80° C. for 1 h, cooled and mixed with a saturated aqueous solution of sodium bicarbonate (50 mL) and extracted with ethyl acetate (3×50 mL). The combined extracts were dried over magnesium sulfate, filtered and evaporated to dryness. Chromatography on silica eluting with a gradient of 20% to 30% EtOAc/hexane gave an oil (0.056 g, 19%): LCMS (+APCI) 368 (M+H).

Workup

  1. temperaturecooled
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. dry with materialThe combined extracts were dried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-4e80aec3e07c4cb4a988a993cbb6b46f
Source dataset
uspto-grants-2008_09
Patent number
US07425572B2

Reaction notes

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