Ethylbenzene → 1-[3-(2-Hydroxy-3,3-dimethylpentyl)-5-methoxy-1-benzofuran-2-yl]-2,2-dimethylpropan-1-one

HRID 2103776ノート

反応式

HRID 2103776 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[C:8]([CH3:17])[C:7]=2[CH:18]=1.[Li+].CC([N-]C(C)C)C.C(C1C=CC=CC=1)C.[CH3:35][C:36]([CH3:41])([CH2:39][CH3:40])[CH:37]=[O:38]>C1COCC1.CCCCCCC>[OH:38][CH:37]([C:36]([CH3:41])([CH3:35])[CH2:39][CH3:40])[CH2:17][C:8]1[C:7]2[CH:18]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=2[O:10][C:9]=1[C:11](=[O:16])[C:12]([CH3:13])([CH3:14])[CH3:15]

参加物

7

反応物 4

HCID 7500EthylbenzeneHCID 137426Butanal, 2,2-dimethyl-HCID 2724682Lithium diisopropylamideHCID 288262421-(5-Methoxy-3-methyl-1-benzofuran-2-yl)-2,2-dimethylpropan-1-one

生成物 1

HCID 689512471-[3-(2-Hydroxy-3,3-dimethylpentyl)-5-methoxy-1-benzofuran-2-yl]-2,2-dimethylpropan-1-one

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8900Heptane溶媒

実験手順

To a solution of 0.493 g 1-(5-methoxy-3-methyl-1-benzofuran-2-yl)-2,2-dimethylpropan-1-one from Step A Example 1 in 20 mL anhydrous THF at −78° C. under nitrogen was added 2.0 mL 2 M LDA in heptane, THF, and ethylbenzene. After 50 minutes, 0.40 g 2,2-dimethylbutanal was added. Remove the cooling bath and let the reaction mixture warm up to room temperature. After 70 minutes, the reaction was quenched by adding 2 mL saturated ammonium chloride and the reaction mixture was evaporated under reduced pressure to remove solvents. Dilute the residue with ether, wash with 1 M HCl (2×) and saturated brine, dry over anhydrous Na2SO4, and evaporate to give a crude product. It was purified on RP-HPLC using 65˜100% MeCN in water without TFA to give the title compound as colorless solid after lyophilization. 1H NMR (CDCl3, 500 MHz) 7.44 (d, 9.1 Hz, 1H), 7.20 (d, 2.0 Hz, 1H), 7.10 (dd, 2.5 & 9.1 Hz, 1H), 3.86 (s, 3H), 3.58 (dd, 1.6 & 10.6 Hz, 1H), 3.29˜3.34 (m, 1H), 2.90˜2.95 (m, 1H), 1.51˜1.59 (m, 1H), 1.39˜1.46 (m, 1H), 1.40 (s, 9H), 1.02 (s, 3H), 1.01 (s, 3H), 0.92 (t, 7.6 Hz, 3H). LC-MS: 4.47 min. (m/Z=329.3, 369.2, 347). A faster-eluting isomeric side-product was also isolated during purification and was identified as 1-[2-(1-hydroxy-2,2-dimethylpropyl)-5-methoxy-1-benzofuran-3-yl]-3,3-dimethylpentan-2-one. 1H NMR (CDCl3, 500 MHz) 7.30 (d, 9.0 Hz, 1H), 6.84 (dd, 2.5 & 8.9 Hz, 1H), 6.75 (d, 2.5 Hz, 1H), 4.44 (s, 1H), 4.07 (AB d, 18.5 Hz, 1H), 4.04 (AB d, 18.5 Hz, 1H), 3.78 (s, 3H). 1.74 (q, 7.6 Hz, 2H), 1.263 (s, 3H), 1.260 (s, 3H), 0.99 (s, 9H), 0.91 (t, 7.4 Hz, 3H). LC-MS: 3.95 min. (m/Z=369.3=M+Na, 329.3,).

後処理

  1. customRemove the cooling bath
  2. waitAfter 70 minutes
  3. customthe reaction was quenched
  4. additionby adding 2 mL saturated ammonium chloride
  5. customthe reaction mixture was evaporated under reduced pressure
  6. customto remove solvents
  7. additionDilute the residue with ether
  8. washwash with 1 M HCl (2×) and saturated brine
  9. dry with materialdry over anhydrous Na2SO4
  10. customevaporate
  11. customto give a crude product
  12. customIt was purified on RP-HPLC

出典と根拠

ORDレコード
ord-0374708865424ef1a1aa218ca761f62c
出典データセット
uspto-grants-2009_08
特許番号
US07576122B2

反応ノート

読み込み中…