Acetic Acid → Methyl 2-(chroman-6-ylmethylene)-3-oxobutanoate

HRID 1912540ノート

反応式

HRID 1912540 の反応式
[O:1]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]=O)=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[O:13]=[C:14]([CH3:20])[CH2:15][C:16]([O:18][CH3:19])=[O:17].N1CCCCC1.CC(O)=O>C1C=CC=CC=1>[O:1]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]=[C:15]([C:14](=[O:13])[CH3:20])[C:16]([O:18][CH3:19])=[O:17])=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1

参加物

6

反応物 4

HCID 176Acetic AcidHCID 7757Methyl acetoacetateHCID 8082PiperidineHCID 6504215Chroman-6-carbaldehyde

生成物 1

HCID 78036909Methyl 2-(chroman-6-ylmethylene)-3-oxobutanoate収率 60.47%

試薬・触媒・溶媒 1

HCID 241Benzene溶媒

実験手順

A solution of 6-iodochroman (13.8 g, 53.1 mmol) in tetrahydrofuran (THF) (143 mL) was cooled to −78° C. in a dry ice/acetone bath and then treated with n-BuLi, 2.5M solution in hexanes (23.35 mL, 58.4 mmol). The mixture was stirred for 10 minutes before being treated with N,N-dimethylformamide (6.16 mL, 80 mmol) and the resultant was warmed to ambient temperature and stirred for 10 minutes. The mixture was quenched with saturated NH4Cl and extracted with ethyl acetate. The extracts were washed with brine, dried over Na2SO4, filtered and concentrated to afford the crude chroman-6-carbaldehyde as a yellow solid which was used without further purification. LC/MS (m/z) ES+=163.22 (M+1). A solution of the crude chroman-6-carbaldehyde, methyl 3-oxobutanoate, piperidine (0.263 mL, 2.66 mmol) and AcOH (0.152 mL, 2.66 mmol) in Benzene (113 mL) was refluxed (DS-trap) overnight. The mixture was concentrated and diluted with ethyl acetate. The dilution was washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel (0-30% hexanes/ethyl acetate) the afford methyl 2-(chroman-6-ylmethylene)-3-oxobutanoate (mixture of E and Z isomers, 8.352 g, 32.08 mmol, 60.47% yield) as a thick yellow oil. 1H NMR (400 MHz, CHLOROFORM-d, major isomer) δ ppm 7.48 (s, 1 H), 7.22-7.12 (m, 2 H), 6.78 (d, J=8.6 Hz, 1 H), 4.27-4.18 (m, 2 H), 3.92-3.81 (m, 3 H), 2.77 (t, J=6.3 Hz, 2 H), 2.39 (s, 3 H), 2.06-1.99 (m, 2 H); 1H NMR (400 MHz, CHLOROFORM-d, minor isomer) δ ppm 7.58 (s, 1 H), 7.16-7.08 (m, 2 H), 6.79-6.71 (m, 1 H), 4.23-4.18 (m, 2 H), 3.84-3.78 (m, 3 H), 2.76 (t, J=6.4 Hz, 2 H), 2.38 (s, 3 H), 2.03-1.96 (m, 2 H); LC/MS (m/z) ES+=261.2 (M+1).

後処理

  1. customwas used without further purification
  2. concentrationThe mixture was concentrated
  3. additiondiluted with ethyl acetate
  4. washThe dilution was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-b98ade996d4f4af59701cdc4ebf22703
出典データセット
uspto-grants-2013_12
特許番号
US08609653B2

反応ノート

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