Methyl 3-mercaptopropionate → Methyl 3-[[(4-methoxy)-tetrahydro-pyran-4-yl]phenylmethylthio]propionate

HRID 890887Notes

Reaction equation

HRID 890887 reaction equation
[CH3:1][O:2][C:3]1([C:9]2[CH:10]=[C:11](CBr)[CH:12]=[CH:13][CH:14]=2)[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[SH:17][CH2:18][CH2:19][C:20]([O:22][CH3:23])=[O:21].[CH2:24]1CCN2C(=NCCC2)CC1>C1COCC1.C(OCC)(=O)C>[CH3:1][O:2][C:3]1([CH:9]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:24]=2)[S:17][CH2:18][CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH2:4][CH2:5][O:6][CH2:7][CH2:8]1

Participants

6

Reactant 3

HCID 18050Methyl 3-mercaptopropionateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 102659323-[(4-Methoxy)tetrahydropyran-4-yl)-alpha-bromotoluene

Product 1

HCID 54047158Methyl 3-[[(4-methoxy)-tetrahydro-pyran-4-yl]phenylmethylthio]propionateYield 75%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

A solution of 3-[(4-methoxy)tetrahydropyran-4-yl)-α-bromotoluene (1.0 g, 3.87 mmol) in 10 mL of anhydrous THF was cooled to 5° C. A solution of methyl 3-mercaptopropionate (0.46 g, 3.87 mmol) and DBU (0.59 g, 3.87 mmol) in 10 mL of THF was added while maintaining the temperature at 5° C. The reaction mixture was stirred for 1 h at 5° C. and for 18 h at room temperature. The reaction mixture was diluted with 200 mL of ethyl acetate, and this solution was washed with 1 N HCl (1×100 mL), saturated sodium bicarbonate (1×100 mL), brine (1×100 mL), dried over magnesium sulfate, filtered and concentrated. The concentrated residue was purified by flash column chromatography on silica gel, eluting with 20% ethyl acetate in hexane, to give 0.94 g (75%) of methyl 3-[[(4-methoxy)-tetrahydro-pyran-4-yl]phenylmethylthio]propionate as a pink oil: 1H NMR (CDCl3/300 MHz) δ 1.93–2.09 (m, 4H), 2.54 (t, 2H, J=7.4 Hz), 2.68 (t, 2H, J=7.5 Hz), 2.97 (s, 3H), 3.68 (s, 3H), 3.75 (s, 2H), 3.80–3.92 (m, 4H), 7.23–7.36 (m, 4H). HRMS calcd for C17H24O4S 325.1474. Found 325.1494.

Workup

  1. washthis solution was washed with 1 N HCl (1×100 mL), saturated sodium bicarbonate (1×100 mL), brine (1×100 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe concentrated residue was purified by flash column chromatography on silica gel
  6. washeluting with 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-0bdd71ff9875476e8011c5b58dea9f34
Source dataset
uspto-grants-2006_02
Patent number
US06998415B2

Reaction notes

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