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

HRID 1172895

Reaction equation

HRID 1172895 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:31])[CH:9]([C:17]1[CH:30]=[CH:29][C:20]2[CH:21]=[C:22]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[S:23][C:19]=2[CH:18]=1)[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])([CH3:6])([CH3:5])[CH3:4].CN(C=O)C.[B-](F)(F)(F)[F:38].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>C1COCC1>[C:3]([O:7][C:8](=[O:31])[C:9]([C:17]1[CH:30]=[CH:29][C:20]2[CH:21]=[C:22]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[S:23][C:19]=2[CH:18]=1)([F:38])[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])([CH3:4])([CH3:5])[CH3:6]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 2724933SelectfluorHCID 59424236Di-tert-butyl [2-(ethoxycarbonyl)-1-benzothien-6-yl]malonate

Product 1

HCID 59556415Di-tert-butyl [2-(ethoxycarbonyl)-1-benzothien-6-yl](fluoro)malonate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of sodium hydride (0.96 g, 24.0 mmol) in THF (75 mL) cooled to 0° C. was added a solution of di-tert-butyl[2-(ethoxycarbonyl)-1-benzothien-6-yl]malonate (described above) (9.66 g, 23.0 mmol) in THF (150 mL) under nitrogen. The resulting orange solution was stirred at 4° C. for 15 minutes. DMF (225 mL) was added followed by Selectfluor (8.15 g, 23.0 mmol). The reaction was warmed to ambient temperature and stirred for 4 hours under nitrogen. The reaction was quenched with ammonium chloride solution and partitioned between ethyl acetate and water. The organics were washed with water and brine, dried over magnesium sulfate, filtered and evaporated in vacuo. Purification by flash column chromatography (2-20% ethyl acetate/hexanes) gave a mixture of starting material and product. This was resubjected to above reaction conditions and purified in a similar manner to give a pale yellow solid. 1H NMR (DMSO-d6) δ 8.21 (s, 1H), 8.17 (s, 1H), 8.07 (d, J=8.8 Hz, 1H), 7.52 (d, J=9.1 Hz, 1H), 4.33 (q, J=7.3 Hz, 2H), 1.44 (s, 18H), 1.31 (t, J=7.0 Hz, 3H).

Workup

  1. temperatureThe reaction was warmed to ambient temperature
  2. stirringstirred for 4 hours under nitrogen
  3. customThe reaction was quenched with ammonium chloride solution
  4. custompartitioned between ethyl acetate and water
  5. washThe organics were washed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customPurification by flash column chromatography (2-20% ethyl acetate/hexanes)
  10. customgave
  11. additiona mixture of starting material and product
  12. customThis was resubjected to above reaction conditions
  13. custompurified in a similar manner
  14. customto give a pale yellow solid

Sources & evidence

ORD record
ord-ddc6c742827d4b5797d9d4cbd4649564
Source dataset
uspto-grants-2010_11
Patent number
US07834034B2

Linked notes

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