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

HRID 2084535노트

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HRID 2084535 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-40 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-f28a55a056ae4b758565c16dbc9a7124
출처 데이터셋
uspto-grants-2004_04
특허 번호
US06716878B1

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