Water → Methyl 6-(cyclobutylmethylene)-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate

HRID 505703

반응식

HRID 505703 반응식
[O:1]=[C:2]1[CH2:11][CH2:10][CH2:9][C:8]2[CH:7]=[C:6]([C:12]([O:14][CH3:15])=[O:13])[CH:5]=[CH:4][C:3]1=2.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH:26]1([CH:30]=O)[CH2:29][CH2:28][CH2:27]1.O>O1CCCC1>[CH:26]1([CH:30]=[C:11]2[CH2:10][CH2:9][C:8]3[CH:7]=[C:6]([C:12]([O:14][CH3:15])=[O:13])[CH:5]=[CH:4][C:3]=3[C:2]2=[O:1])[CH2:29][CH2:28][CH2:27]1

참가 물질

6

반응물 4

HCID 962WaterHCID 2733832Lithium HexamethyldisilazideHCID 12431621CyclobutanecarbaldehydeHCID 15309116Methyl 5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate

생성물 1

HCID 66722983Methyl 6-(cyclobutylmethylene)-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate수율 38%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A solution of methyl 5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate (600 mg, 2.9 mmol) in tetrahydrofuran (10 mL) was cooled to ice bath temperature and treated with 1.0 M lithium hexamethyldisilazide in tetrahydrofuran (5 mL). After stirring for twenty minutes, cyclobutanecarboxaldehyde (J. Med. Chem. 1989, 32, 1001-6) (24 mL of 0.5 M solution in tetrahydrofuran) was slowly added and the mixture allowed to warm to room temperature and stir for 3 days. The mixture was poured into water, extracted three times with ethyl acetate, washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude product was purified by normal phase flash column chromatography on a 50 g silica gel column (5-50% ethyl acetate/hexanes gradient). Pure fractions were pooled and concentrated in vacuo to yield methyl 6-(cyclobutylmethylene)-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate (300 mg, 1.1 mmol, 38% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.81-2.03 (m, 4H), 2.14-2.27 (m, 2H), 2.71 (t, J=6.58 Hz, 2H), 2.93-3.00 (m, 2H), 3.34-3.44 (m, 1H), 3.88 (s, 3H), 6.91 (d, J=9.13 Hz, 1H), 7.84-7.95 (m, 2H), 8.01 (d, J=8.06 Hz, 1H). ES-MS m/z 271 (M+H).

후처리

  1. stirringstir for 3 days
  2. extractionextracted three times with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by normal phase flash column chromatography on a 50 g silica gel column (5-50% ethyl acetate/hexanes gradient)
  8. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-718c348b559248ab8bbae3702806f80b
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07781428B2

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