Water → Di-tert-butyl [2-(ethoxycarbonyl)-1-benzothien-6-yl](methyl)malonate

HRID 500664Notes

Reaction equation

HRID 500664 reaction equation
[H-].[Na+].[SH:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].F[C:11]1[CH:12]=[C:13]([C:19]([CH3:34])([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:14]=[CH:15][C:16]=1[CH:17]=O.O>CS(C)=O>[CH2:8]([O:7][C:5]([C:4]1[S:3][C:11]2[CH:12]=[C:13]([C:19]([CH3:34])([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:27]([O:29][C:30]([CH3:33])([CH3:31])[CH3:32])=[O:28])[CH:14]=[CH:15][C:16]=2[CH:17]=1)=[O:6])[CH3:9]

Participants

6

Reactant 4

HCID 962WaterHCID 12185Ethyl ThioglycolateHCID 24758Sodium hydrideHCID 57443966Di-tert-butyl (3-fluoro-4-formylphenyl)(methyl)malonate

Product 1

HCID 59424240Di-tert-butyl [2-(ethoxycarbonyl)-1-benzothien-6-yl](methyl)malonateYield 22%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

Sodium hydride (60% dispersion in mineral oil, 0.19 g, 4.75 mmol) was suspended in DMSO (2.5 mL) and ethyl mercaptoacetate (0.28 mL, 2.54 mmol) was added portionwise using a water bath to moderate the exotherm. On complete addition, the water bath was removed and stirring continued for 15 minutes. A solution of di-tert-butyl (3-fluoro-4-formylphenyl)(methyl)malonate (0.81 g, 2.30 mmol) in DMSO (0.5 mL) was added in one portion. The orange solution was warmed with a heat gun to give a dark brown solution. H2O was added (150 mL) and the products were extracted into EtOAc (2×100 mL). The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by MPLC gave 0.22 g of desired product (pale yellow solid, 22%). 1H NMR (CDCl3) δ 8.01 (s, 1H), 7.88 (d, J=1.8 Hz, 1H), 7.81 (d, J=8.4 Hz, 1H), 7.48 (dd, J=8.4, 1.8 Hz, 1H), 4.39 (q, J=7.2 Hz, 2H), 1.84 (s, 3H), 1.47 (s, 18H), 1.40 (t, J=7.2 Hz, 3H).

Workup

  1. additionOn complete addition
  2. customthe water bath was removed
  3. temperatureThe orange solution was warmed with a heat gun
  4. customto give a dark brown solution
  5. extractionthe products were extracted into EtOAc (2×100 mL)
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by MPLC

Sources & evidence

ORD record
ord-4d5cc27dcc7542c7b1d2f984e482e21f
Source dataset
uspto-grants-2010_08
Patent number
US07772238B2

Reaction notes

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