Sodium hydride → tert-Butyl 2-(6-(cyanomethoxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate

HRID 1798118Notes

Reaction equation

HRID 1798118 reaction equation
[OH:1][B:2]1[C:6]2[CH:7]=[C:8]([OH:12])[CH:9]=[C:10]([CH3:11])[C:5]=2[CH:4]([CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[O:3]1.[H-].[Na+].I[CH2:24][C:25]#[N:26]>CN(C=O)C>[C:25]([CH2:24][O:12][C:8]1[CH:9]=[C:10]([CH3:11])[C:5]2[CH:4]([CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[O:3][B:2]([OH:1])[C:6]=2[CH:7]=1)#[N:26]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 69356IodoacetonitrileHCID 58292793tert-Butyl 2-(1,6-dihydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate

Product 1

HCID 67254401tert-Butyl 2-(6-(cyanomethoxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetateYield 21%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of tert-butyl 2-(1,6-dihydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate (500 mg, 1.80 mmol) in DMF (10 mL) was added 60% NaH (215.8 mg, 5.40 mmol) in DMF (5 mL) at 0° C. The reaction mixture was stirred for 30 min, followed by addition of 2-iodoacetonitrile (450.5 mg, 2.70 mmol). The reaction mixture was stirred for an additional 5 h at room temperature, quenched by water (15 mL) at 0° C., and acidified by 1N HCl to pH=7. The resulting mixture was extracted by EtOAc (3×10 mL) and the combined organic layers were dried over anhydrous Na2SO4 and concentrated to dryness. The residue was purified by prep HPLC to give the title compound as a white solid (120 mg, yield: 21%).

Workup

  1. stirringThe reaction mixture was stirred for an additional 5 h at room temperature
  2. customquenched by water (15 mL) at 0° C.
  3. extractionThe resulting mixture was extracted by EtOAc (3×10 mL)
  4. dry with materialthe combined organic layers were dried over anhydrous Na2SO4
  5. concentrationconcentrated to dryness
  6. customThe residue was purified by prep HPLC

Sources & evidence

ORD record
ord-d421c9dff5ac4b8ba75bbc30a8a72bcc
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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