Hydrochloric Acid → 2-(3-(Hydroxymethyl)-6-nitro-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)acetonitrile

HRID 1444807Notes

Reaction equation

HRID 1444807 reaction equation
[N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[O:12][CH2:11][CH:10]([CH2:13][OH:14])[O:9][C:8]=2[CH:15]=1)([O-:3])=[O:2].ClC1C=CC(O[CH2:22][C:23]#[N:24])=CC=1.CC(C)([O-])C.[K+].Cl>CN(C=O)C.O>[OH:14][CH2:13][CH:10]1[CH2:11][O:12][C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[C:15]([CH2:22][C:23]#[N:24])[C:8]=2[O:9]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3064442-(4-Chlorophenoxy)acetonitrileHCID 12736685(7-Nitro-2,3-dihydro-1,4-benzodioxin-2-yl)methanolHCID 23665647Potassium tert-butoxide

Product 1

HCID 236531902-(3-(Hydroxymethyl)-6-nitro-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)acetonitrileYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-2.5 °C

Procedure

A solution of racemic (7-nitro-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methanol (1.00 g, 4.73 mmol) and 4-chlorophenoxyacetonitrile (827 mg, 4.94 mmol) in DMF (12 mL) was added dropwise to a solution of potassium tert-butoxide (2.12 g, 18.9 mmol) in DMF (20 mL) at −5-0° C. After the addition was complete (7 minutes), the reaction mixture was stirred for 1 hour at −5-0° C. The reaction mixture was acidified with 1 N HCl before drowning into water (200 mL). The mixture was extracted with EtOAc (3×100 mL) and the combined organic layers were washed with 1N NaOH (3×50 mL) to remove most of the 4-chlorophenol. After removal of solvent, the residue was purified by flash chromatography on silica gel, gradient elution using 2:3, 1:1, 3:2, 100:0 ethyl acetate/hexane, to give 139 mg, 14% recovered starting material and 804 mg, 68% yield of the title compound as a solid. 1H NMR (CDCl3) δ 7.77 (1H, d, J=9.12 Hz); 7.01 (1H, d, J=9.12 Hz); 4.50-4.40 (2H, m); 4.30-3.91 (5H, m); 2.25-2.21 (1H, m). 13C NMR (CDCl3) δ 148.07, 141.71, 141.55, 119.44, 117.07, 116.96, 115.71, 74.36, 65.31, 61.18, 14.89.

Workup

  1. additionAfter the addition
  2. custom(7 minutes)
  3. extractionThe mixture was extracted with EtOAc (3×100 mL)
  4. washthe combined organic layers were washed with 1N NaOH (3×50 mL)
  5. customto remove most of the 4-chlorophenol
  6. customAfter removal of solvent
  7. customthe residue was purified by flash chromatography on silica gel, gradient elution
  8. customto give 139 mg, 14%
  9. customrecovered

Sources & evidence

ORD record
ord-dd5025c229f141a181568df45274d476
Source dataset
uspto-grants-2010_02
Patent number
US07662979B2

Reaction notes

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