1,4-Cyclohexadiene → [(2S)-7-nitro-2,3-dihydro-1,4-benzodioxin-2-yl]methanol

HRID 1259446Notes

Reaction equation

HRID 1259446 reaction equation
C([O:8][C:9]1[CH:19]=[C:18]([N+:20]([O-:22])=[O:21])[CH:17]=[CH:16][C:10]=1[O:11][CH2:12][C@H:13]1[CH2:15][O:14]1)C1C=CC=CC=1.C(=O)(O)[O-].[Na+].C1CC=CCC=1>CCO>[N+:20]([C:18]1[CH:17]=[CH:16][C:10]2[O:11][CH2:12][C@H:13]([CH2:15][OH:14])[O:8][C:9]=2[CH:19]=1)([O-:22])=[O:21]

Participants

5

Reactant 3

HCID 123431,4-CyclohexadieneHCID 516892Sodium BicarbonateHCID 25019918(2R)-2-{[2-(benzyloxy)-4-nitrophenoxy]methyl}oxirane

Product 1

HCID 25019919[(2S)-7-nitro-2,3-dihydro-1,4-benzodioxin-2-yl]methanolYield 96.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

A 3 L 3-necked flask equipped with a mechanical stirrer, a reflux condenser, a thermocouple and a heating mantel is charged with EtOH (1500 mL), (2R)-2-{[2-(benzyloxy)-4-nitrophenoxy]methyl}oxirane (70.00 g, 0.232 mol), sodium bicarbonate (38.98 g, 0.464 mol) and 1,4-cyclohexadiene (39.56 mL, 0.418 mol). Argon gas is bubbled through the suspension for 5 min, and then the bubbling is discontinued, and palladium (10% on carbon, 4.9 g) is added. The mixture is heated to an internal temperature of 60° C. and stirred at 60° C. for 1 h. The solution is cooled to rt, filtered through a pad of celite and evaporated to dryness. The residue is dissolved in EtOAc (800 mL), and washed with 1 N HCl (2×100 mL) and brine (100 mL), and the volatiles are removed. The title compound (47.33 g, 93%) is obtained as a tan powder. LCMS (Standard Method): 2.23 min, 212 (M+H)+. 1NMR (300 MHz, CDCl3) δ 7.81-7.76 (m, 2H), 6.96 (d, J=8.5 Hz, 1H), 4.42 (dd, J=2.1, 11.2 Hz, 1H), 4.32-4.18 (m, 2H), 3.98-3.85 (m, 2H), 2.03 (br s, 1H).

Workup

  1. customA 3 L 3-necked flask equipped with a mechanical stirrer, a reflux condenser
  2. customArgon gas is bubbled through the suspension for 5 min
  3. additionpalladium (10% on carbon, 4.9 g) is added
  4. temperatureThe solution is cooled to rt
  5. filtrationfiltered through a pad of celite
  6. customevaporated to dryness
  7. dissolutionThe residue is dissolved in EtOAc (800 mL)
  8. washwashed with 1 N HCl (2×100 mL) and brine (100 mL)
  9. customthe volatiles are removed

Sources & evidence

ORD record
ord-1c85cbf7ba3e4ac190b636ee22c03bbc
Source dataset
uspto-grants-2013_06
Patent number
US08466296B2

Reaction notes

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