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

HRID 505703

反応式

HRID 505703 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-718c348b559248ab8bbae3702806f80b
出典データセット
uspto-grants-2010_08
特許番号
US07781428B2

関連ノート

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