Methyl iodide → 4-Methoxy-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

HRID 1501800노트

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HRID 1501800 반응식
[CH3:1][O:2][CH:3]1[C:7]2([CH2:12][CH2:11][N:10](C(OC(C)(C)C)=O)[CH2:9][CH2:8]2)[C:6](=[O:20])[N:5]([C:21]2[CH2:22][O:23][C:24](=[O:27])[C:25]=2[CH3:26])[CH2:4]1.OC1C2(CCN(C(OC(C)(C)C)=O)CC2)C(=O)N(C2COC(=O)C=2C)C1.IC.[Al]>C(#N)C.[Ag]=O>[CH3:1][O:2][CH:3]1[C:7]2([CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[C:6](=[O:20])[N:5]([C:21]2[CH2:22][O:23][C:24](=[O:27])[C:25]=2[CH3:26])[CH2:4]1

참가 물질

7

반응물 4

HCID 6328Methyl iodideHCID 5359268AluminumHCID 86709492tert-Butyl 4-hydroxy-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylateHCID 86709495tert-Butyl 4-methoxy-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate

생성물 1

HCID 899409594-Methoxy-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

시약·촉매·용매 2

HCID 92152Silver(II) oxide촉매HCID 6342Acetonitrile용매

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온도
58 °C

실험 절차

tert-Butyl 4-methoxy-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate (Enantiomer A and Enantiomer B): To a solution of tert-butyl 4-hydroxy-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate (100 mg, 0.273 mmol) in acetonitrile (1 mL) was added iodomethane (171 μL, 2.73 mmol) and silver oxide (69.6 mg, 0.300 mmol). The vial was sealed, wrapped with aluminum foil, and stirred at 58° C. for 15 h. The reaction mixture was filtered through CELITE®, concentrated to give the crude product, which was purified by column chromatography (0-10% MeOH/DCM) to afford the title compound as a mixture of enantiomers. LC/MS: [(M+1)]+=381. The racemic mixture was separated by SFC-HPLC, using the following conditions: chiralcel AD-H, 2×25 cm, 15% MeOH, 60 mL/min to afford faster eluting Enantiomer A: LC/MS: [(M+1)]+=381; and slower eluting Enantiomer B: LC/MS: [(M+1)]+=381

후처리

  1. customThe vial was sealed
  2. filtrationThe reaction mixture was filtered through CELITE®
  3. concentrationconcentrated
  4. customto give the crude product, which
  5. customwas purified by column chromatography (0-10% MeOH/DCM)

출처 및 근거

ORD 기록
ord-6dd607733de34e7b82d2dab3e8b7b2f7
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206198B2

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