Hydrochloric Acid → (Z)-ethyl 3-(5-(benzyloxy)-2-methoxyphenyl)-3-(5-methylthiazol-2-yl)acrylate

HRID 1496983Notes

Reaction equation

HRID 1496983 reaction equation
[H-].[Na+].C(OP([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])(OCC)=O)C.[CH2:17]([O:24][C:25]1[CH:26]=[CH:27][C:28]([O:39][CH3:40])=[C:29]([C:31]([C:33]2[S:34][C:35]([CH3:38])=[CH:36][N:37]=2)=O)[CH:30]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.Cl>C1COCC1.O>[CH2:17]([O:24][C:25]1[CH:26]=[CH:27][C:28]([O:39][CH3:40])=[C:29](/[C:31](/[C:33]2[S:34][C:35]([CH3:38])=[CH:36][N:37]=2)=[CH:11]/[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:30]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 117600565(5-(Benzyloxy)-2-methoxyphenyl)(5-methylthiazol-2-yl)methanone

Product 1

HCID 117620109(Z)-ethyl 3-(5-(benzyloxy)-2-methoxyphenyl)-3-(5-methylthiazol-2-yl)acrylateYield 58%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a suspension of NaH (60%, 884 mg, 22.1 mmol) in dry THF (120 mL) was added ethyl 2-(diethoxyphosphoryl)acetate (4.96 g, 22.1 mmol) at −78° C. After being stirred at −78° C. for 1 hour, a solution of (5-(benzyloxy)-2-methoxyphenyl)(5-methylthiazol-2-yl)methanone (2.50 g, 7.37 mmol) in THF (30 mL) was added drop wise over 30 min. The mixture was stirred at −78° C. for 30 min and then warmed to room temperature with stirring overnight. The mixture was cooled to 0° C. and treated with water (50 mL), pH value was adjusted to 6 with HCl (0.5 N). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with petroleum ether/EtOAc (3:1) to afford (Z)-ethyl 3-(5-(benzyloxy)-2-methoxyphenyl)-3-(5-methylthiazol-2-yl)acrylate (1.75 g, 58.0%) as yellow gel.

Workup

  1. stirringThe mixture was stirred at −78° C. for 30 min
  2. temperaturewarmed to room temperature
  3. stirringwith stirring overnight
  4. temperatureThe mixture was cooled to 0° C.
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with petroleum ether/EtOAc (3:1)

Sources & evidence

ORD record
ord-28980d3856644f408028cfd8f4a70238
Source dataset
uspto-grants-2015_12
Patent number
US09199947B2

Reaction notes

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