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

HRID 1172878Notes

Reaction equation

HRID 1172878 reaction equation
[C:1]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])(=[O:10])[CH2:2][C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[H-].[Na+].Br[C:19]1[CH:32]=[CH:31][C:22]2[CH:23]=[C:24]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[S:25][C:21]=2[CH:20]=1.[NH4+].[Cl-]>C1COCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[C:12]([O:11][C:1](=[O:10])[CH:2]([C:19]1[CH:32]=[CH:31][C:22]2[CH:23]=[C:24]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[S:25][C:21]=2[CH:20]=1)[C:3]([O:5][C:6]([CH3:7])([CH3:8])[CH3:9])=[O:4])([CH3:15])([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 68324Di-tert-butyl malonateHCID 13567982Ethyl 6-bromo-1-benzothiophene-2-carboxylate

Product 1

HCID 59424236Di-tert-butyl [2-(ethoxycarbonyl)-1-benzothien-6-yl]malonate

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Di-tert-butyl malonate (1.5 g, 6.93 mmol) was dissolved in THF (6 mL) and sodium hydride (60% dispersion in mineral oil, 0.28 g, 7.00 mmol) was added. The mixture was stirred for 10 minutes before adding Pd(PtBu3)2 (0.1 g, 0.196 mmol) and a solution of ethyl 6-bromo-1-benzothiophene-2-carboxylate (1.8 g, 6.3 mmol) in THF (12 mL). The resulting mixture was heated to reflux under N2 for 18 hours. Room temperature was attained, saturated NH4Cl (150 mL) was added and the products extracted into EtOAc (2×125 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. Purification of the residue by MPLC gave the desired product (pale yellow solid). 1H NMR (DMSO-d6) δ 8.17 (s, 1H), 8.01 (s, 1H), 7.99 (d, J=8.4 Hz, 1H), 7.45 (dd, J=8.4, 1.8 Hz, 1H), 4.83 (s, 1H), 4.33 (q, J=7.2 Hz, 2H), 1.40 (s, 18H), 1.31 (t, J=7.2 Hz, 3H).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux under N2 for 18 hours
  3. customRoom temperature
  4. extractionthe products extracted into EtOAc (2×125 mL)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by MPLC

Sources & evidence

ORD record
ord-874cd5155dad42a5b5e3fada175bd5b8
Source dataset
uspto-grants-2010_11
Patent number
US07834034B2

Reaction notes

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