تفاعل #160215

ord-4ff4a8cf9f464d6d9c7229379c5ccfbb

المذيبات

ظروف التفاعل

درجة الحرارة
75°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    workup.STIRRINGthe reaction mixture was stirred for 3 hours
  2. 2
    ترشيحfiltered
  3. 3
    تركيزconcentrated in vacuo
  4. 4
    أخرىThe residue was purified by silica gel column chromatography
  5. 5
    أخرىto give the ether intermediate as pale yellow oil
  6. 6
    ترشيحThe reaction mixture was filtered
  7. 7
    تركيزconcentrated in vacuo
  8. 8
    workup.ADDITIONdiluted with ethyl acetate
  9. 9
    غسيلwashed with 1:1 3M NaOH/
  10. 10
    تجفيفaq. NaHCO3, dried over MgSO4
  11. 11
    ترشيحfiltered
  12. 12
    تركيزconcentrated in vacuo

الإجراء التجريبي

To [8-benzyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone hydrochloride salt (43 mg, 0.09 mmol) in DMF (0.5 mL) was added sodium hydride (11 mg, 0.30 mmol) and the reaction mixture was stirred for 20 minutes. Iodoethane (30 μL, 0.38 mmol) was added and the reaction mixture was stirred for 3 hours, then diluted with EtOAc, filtered, concentrated in vacuo. The residue was purified by silica gel column chromatography using 10-100 EtOAc/hexanes eluent to give the ether intermediate as pale yellow oil. The oil was dissolved in methanol (0.6 mL), and Pd (5 mg, 0.004 mmol) and ammonium formate (27 mg, 0.44 mmol) were added and the reaction mixture was heated at 75° C. for 40 minutes. The reaction mixture was filtered, concentrated in vacuo, diluted with ethyl acetate, washed with 1:1 3M NaOH/sat. aq. NaHCO3, dried over MgSO4, filtered and concentrated in vacuo to give [10-(ethoxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (25 mg, 74%) as a pale yellow oil. ESI-MS m/z calc. 390.5. Found 391.3 (M+1)+; Retention time: 1.17 minutes (3 min run).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08828996B2uspto-grants-2014_09