Sodium Carbonate → (S)-1-(5-methoxy-2,3-dihydro-benzofuran-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol

HRID 278434ノート

反応式

HRID 278434 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[O:10][C@H:9]([CH2:11]OS(C3C(C)=CC=CC=3)(=O)=O)[CH2:8][C:7]=2[CH:23]=1.[CH3:24][C:25]1[CH:38]=[CH:37][C:28]([CH2:29][C:30]2([OH:36])[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)=[CH:27][CH:26]=1.C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl.CO>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[O:10][C@H:9]([CH2:11][N:33]3[CH2:34][CH2:35][C:30]([CH2:29][C:28]4[CH:27]=[CH:26][C:25]([CH3:24])=[CH:38][CH:37]=4)([OH:36])[CH2:31][CH2:32]3)[CH2:8][C:7]=2[CH:23]=1

参加物

6

反応物 4

HCID 10340Sodium CarbonateHCID 105362424-(4-Methylbenzyl)-piperidin-4-olHCID 21226129Dichloromethane methanolHCID 88124042(S)-Toluenesulfonic acid 5-methoxy-2,3-dihydro-benzofuran-2-ylmethyl ester

生成物 1

HCID 18710240(S)-1-(5-methoxy-2,3-dihydro-benzofuran-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol収率 87.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
110 °C

実験手順

(S)-Toluenesulfonic acid 5-methoxy-2,3-dihydro-benzofuran-2-ylmethyl ester (2.30g, 6.88 mmol) and 4-(4-methyl-benzyl)-piperidin-4-ol (1.62 g, 7.9 mmol) and Na2CO3 (1.10 g, 10.3 mmol) were suspended in DMF and heated at 110° C. for 1 hr. After cooling to ambient temperature distilled H2O and EtOAc were added (100 ml) and the mixture shaken, the organic phase was then separated and the aqueous phase extracted with EtOAc (10 ml). The combined organic extracts were then washed with satd. NaCl solution (100 ml) and the organic phase dried with Na2SO4, filtered and evaporated to afford a yellow oil. This foam was chromatographed over SiO2 (Merck 230-400 mesh) with CH2Cl2, and then with CH2Cl2—MeOH (97:3) to afford (S)-1-(5-methoxy-2,3-dihydro-benzofuran-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol (2.20 g, 6.0 mmol, 87% yield) as a yellow oil MS: m/e=368.2 (M+H+) [α]=+45.8° (c=1.0, CHCl3).

後処理

  1. temperatureAfter cooling to ambient temperature
  2. distillationdistilled H2O and EtOAc
  3. additionwere added (100 ml)
  4. customthe organic phase was then separated
  5. extractionthe aqueous phase extracted with EtOAc (10 ml)
  6. washThe combined organic extracts were then washed with satd
  7. dry with materialNaCl solution (100 ml) and the organic phase dried with Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customto afford a yellow oil
  11. customThis foam was chromatographed over SiO2 (Merck 230-400 mesh) with CH2Cl2

出典と根拠

ORDレコード
ord-fa72a7a00fba49be89ec41f6cb2a910c
出典データセット
uspto-grants-2002_03
特許番号
US06359138B1

反応ノート

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