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

HRID 1172886Notes

Reaction equation

HRID 1172886 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>[C:30]([O:29][C:27](=[O:28])[C:19]([C:13]1[CH:14]=[CH:15][C:16]2[CH:17]=[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[S:3][C:11]=2[CH:12]=1)([CH3:34])[C:20]([O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:21])([CH3:31])([CH3:32])[CH3:33]

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)malonate

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 L) 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 the desired product (pale yellow solid). 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-c9adc3da067c499da555d6634f3255d1
Source dataset
uspto-grants-2010_11
Patent number
US07834034B2

Reaction notes

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