Benzaldehyde → (+/-)-{(2R*,4S*)-1-[(1R*)-4-Methyl-1-phenylpent-4-en-2-yn-1-yl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetic acid

HRID 1869758ノート

反応式

HRID 1869758 の反応式
C[CH:2]([C@H:6]1[CH2:11][CH2:10][NH:9][C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)[CH2:7]1)[C:3]([O-:5])=[O:4].[CH:22](=O)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.O.[CH3:31][C:32]([C:34]#[CH:35])=[CH2:33]>CO.[Au](Br)(Br)Br>[CH3:33][C:32](=[CH2:31])[C:34]#[C:35][C@H:22]([N:9]1[CH2:10][CH2:11][C@H:6]([CH2:2][C:3]([OH:5])=[O:4])[CH2:7][C@@H:8]1[C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:20])([F:19])[F:21])=[CH:14][CH:13]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

参加物

7

反応物 4

HCID 240BenzaldehydeHCID 962WaterHCID 62323IsopropenylacetyleneHCID 86617998(+/-)-Methyl{(2R*,4S*)-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate

生成物 1

HCID 57987596(+/-)-{(2R*,4S*)-1-[(1R*)-4-Methyl-1-phenylpent-4-en-2-yn-1-yl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetic acid収率 9.5%

試薬・触媒・溶媒 2

HCID 82525Gold tribromide触媒HCID 887Methanol溶媒

反応条件

温度
70 °C

実験手順

(±)-Methyl{(2R*,4S*)-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate (Example 3 Step 3, 150 mg, 0.5 mmol), benzaldehyde (159 mg, 1.5 mmol), gold (III) bromide (22 mg, 0.05 mmol) and water (0.5 ml) were combined in a sealed microwave tube. The mixture was de-gassed and placed under an N2-atmosphere before 2-methyl-1-buten-3-yne (99 mg, 1.5 mmol) was added via syringe, followed by heating to 70° C. using microwave irradiation for 20 min. The reaction mixture was diluted with MeOH and loaded onto a SCX cartridge, which was washed with MeOH, then eluted with 2M ammonia in MeOH. The eluant was treated with 6M aq. NaOH (0.25 ml) and heated to reflux for 2 h. The volatiles were removed under vacuum and the residue partitioned between 2M HCl and DCM. The DCM layer was evaporated and the residue purified by preparative reverse phase HPLC to give 21 mg of the title compound as the TFA salt.

後処理

  1. customThe mixture was de-gassed
  2. additionwas added via syringe
  3. custommicrowave irradiation for 20 min
  4. washwas washed with MeOH
  5. washeluted with 2M ammonia in MeOH
  6. additionThe eluant was treated with 6M aq. NaOH (0.25 ml)
  7. temperatureheated
  8. temperatureto reflux for 2 h
  9. customThe volatiles were removed under vacuum
  10. customthe residue partitioned between 2M HCl and DCM
  11. customThe DCM layer was evaporated
  12. customthe residue purified by preparative reverse phase HPLC

出典と根拠

ORDレコード
ord-e9c228eec1fd4c1db12c580faab9c877
出典データセット
uspto-grants-2009_12
特許番号
US07638629B2

反応ノート

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