Benzofuran → [1(S)-(Benzofuran-2-carbonyl)-2,2-dimethylpropyl]-carbamic Acid tert-butyl Ester

HRID 2084535Notes

Reaction equation

HRID 2084535 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[CH:2]1.C([Li])CCC.[Li]C1OC2C=CC=CC=2C=1.[C:25]([O:29][C:30](=[O:43])[NH:31][C@H:32]([C:37](=[O:42])N(OC)C)[C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:28])([CH3:27])[CH3:26]>C1COCC1>[C:25]([O:29][C:30](=[O:43])[NH:31][C@H:32]([C:37]([C:2]1[O:1][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=1)=[O:42])[C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:28])([CH3:26])[CH3:27]

Participants

6

Reactant 4

HCID 9223BenzofuranHCID 53879830[1(S)-(Methoxy-methyl-carbamoyl)-2,2-dimethylpropyl]-carbamic Acid-tert-butyl EsterHCID 178418339ButyllithiumHCID 178506640HCID 178506640, compound

Product 1

HCID 60077756[1(S)-(Benzofuran-2-carbonyl)-2,2-dimethylpropyl]-carbamic Acid tert-butyl EsterYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

A solution of benzofuran (4.24 g, 36 mmol) in dry THF (20 mL) under argon was cooled to −78° C. n-Butyllithium (22.5 mL, 36 mmol, 1.6M in hexanes) was added dropwise such that an internal temperature below −65° C. was maintained. The reaction was allowed to stir at −78° C. for two hours during which time 2-lithiobenzofuran precipitated as a white solid. The suspension of 2-lithiobenzofuran was added dropwise to a cooled (−78° C.) solution of [1(S)-(Methoxy-methyl-carbamoyl)-2,2-dimethylpropyl]-carbamic acid-tert-butyl ester (3.34 g, 12 mmol) in THF (30 mL) via cannula such that an internal temperature of below −65° C. was maintained. The yellow solution was allowed to stir at −70° C. for 30 minutes and −40° C. for a further 3 hours. The reaction was quenched by addition of saturated ammonium chloride solution (200 mL). The aqueous phase was extracted with ethyl acetate (3×150 mL) and the combined organic extracts washed with brine (2×200 mL), dried over magnesium sulphate, filtered and the solvents removed in vacuo to give a crude yellow oil. Purification by column chromatography (SiO2, 10% ethyl acetate in hexanes) gave the title compound as a yellow solid (3.45 g, 87%).

Workup

  1. additionwas added dropwise such that an internal temperature below −65° C.
  2. temperaturewas maintained
  3. customprecipitated as a white solid
  4. additionThe suspension of 2-lithiobenzofuran
  5. additionwas added dropwise to
  6. temperaturewas maintained
  7. customThe reaction was quenched by addition of saturated ammonium chloride solution (200 mL)
  8. extractionThe aqueous phase was extracted with ethyl acetate (3×150 mL)
  9. washthe combined organic extracts washed with brine (2×200 mL)
  10. dry with materialdried over magnesium sulphate
  11. filtrationfiltered
  12. customthe solvents removed in vacuo
  13. customto give a crude yellow oil
  14. customPurification by column chromatography (SiO2, 10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-f28a55a056ae4b758565c16dbc9a7124
Source dataset
uspto-grants-2004_04
Patent number
US06716878B1

Reaction notes

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