Acetonitrile → 4-((2-Methoxy-4-nitrophenoxy)methyl)tetrahydro-2H-thiopyran-4-ol

HRID 1799792Notes

Reaction equation

HRID 1799792 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:4]=1[O-:12].[K+].OP([O-])(O)=O.[Na+].C(#N)C.[O:23]1[C:25]2([CH2:30][CH2:29][S:28][CH2:27][CH2:26]2)[CH2:24]1>O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:4]=1[O:12][CH2:24][C:25]1([OH:23])[CH2:30][CH2:29][S:28][CH2:27][CH2:26]1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 14144719HCID 14144719, compoundHCID 187531011-Oxa-6-thiaspiro(2.5)octaneHCID 23672064Monosodium phosphate

Product 1

HCID 583877004-((2-Methoxy-4-nitrophenoxy)methyl)tetrahydro-2H-thiopyran-4-olYield 42%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of potassium 2-methoxy-4-nitrophenolate (3.02 g, 14.59 mmol), sodium phosphate monobasic, monohydrate (2.014 g, 14.59 mmol), acetonitrile (12 mL), water (3 mL) and 1-oxa-6-thiaspiro[2.5]octane (1.90 g, 14.59 mmol), prepared as described in patent WO 2005/063729 A1, was heated at 150° C. for 3.5 h in a microwave reactor. After cooling to RT, acetonitrile was mostly removed under vacuum, the remaining material was partitioned between EtOAc (100 mL) and H2O (15 mL). The aqueous layer was extracted with EtOAc (2×15 mL) and the combined organic layers were dried (Na2SO4) and evaporated. The residue was purified by flash chromatography (silica gel, hexanes:EtOAc, 100:0 to 60:40) to afford 1.83 g (42%) of the title compound as a yellow solid: 1H NMR (500 MHz, DMSO-d6) δ 7.87 (dd, J=9.07, 2.47 Hz, 1H), 7.73 (d, J=2.75 Hz, 1H), 7.18 (d, J=9.35 Hz, 1H), 4.75 (s, 1H), 3.89 (s, 3H), 3.85 (s, 2H), 2.87-2.97 (m, 2H), 2.49 (s, 1H), 2.38 (d, J=13.20 Hz, 2H), 1.82-1.89 (m, 2H), 1.72-1.82 (m, 2H). HPLC retention time: 2.985 min; LCMS (ES): m/z 282 [M+H]+.

Workup

  1. customprepared
  2. temperatureAfter cooling to RT
  3. customacetonitrile was mostly removed under vacuum
  4. customthe remaining material was partitioned between EtOAc (100 mL) and H2O (15 mL)
  5. extractionThe aqueous layer was extracted with EtOAc (2×15 mL)
  6. dry with materialthe combined organic layers were dried (Na2SO4)
  7. customevaporated
  8. customThe residue was purified by flash chromatography (silica gel, hexanes:EtOAc, 100:0 to 60:40)

Sources & evidence

ORD record
ord-4d07ddf5052142fe95a27924cb2de230
Source dataset
uspto-grants-2013_01
Patent number
US08344160B2

Reaction notes

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