Carbon tetrabromide → (R)-ethyl 4-(4-((4'-chlorobiphenyl-2-yl)(diethoxyphosphoryloxy)methyl)piperidin-1-yl)benzoate

HRID 1476329ノート

反応式

HRID 1476329 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C@H:14]([OH:32])[CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:31]=[CH:30][C:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)=[CH:4][CH:3]=1.C(Br)(Br)(Br)Br.[P:38]([O:45]CC)([O:42][CH2:43][CH3:44])[O:39][CH2:40][CH3:41]>N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C@H:14]([O:32][P:38]([O:42][CH2:43][CH3:44])([O:39][CH2:40][CH3:41])=[O:45])[CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:22]=[CH:23][C:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:30][CH:31]=3)[CH2:17][CH2:16]2)=[CH:6][CH:7]=1

参加物

5

反応物 3

HCID 11205Carbon tetrabromideHCID 31215Triethyl phosphiteHCID 56650671(R)-ethyl 4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoate2 回

生成物 1

HCID 58080102(R)-ethyl 4-(4-((4'-chlorobiphenyl-2-yl)(diethoxyphosphoryloxy)methyl)piperidin-1-yl)benzoate収率 64.1%

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

反応条件

温度
0 °C

実験手順

A solution of (R)-ethyl 4-(4-((4′-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoate (INTERMEDIATE 11A, 600 mg, 1.33 mmol), CBr4 (575 mg, 1.73 mmol), and pyridine (2 ml) at 0° C. was treated dropwise over a 10 minute period with triethyl phosphite (0.56 ml, 3.33 mmol). The solution was stirred at 0° C. for about 10 minutes and then the ice bath was removed. The reaction was stirred overnight at r.t. whereupon the excess pyridine was removed under reduced pressure and the concentrate was taken up in 50 ml of DCM. The organic layer was washed successively with 50 ml each of 0.5 N aq. HCl, saturated aqueous sodium bicarbonate, and water. The organic layers were dried over sodium sulfate, filtered and adsorbed onto silica gel. Purification by column chromatography (ISCO, 80 g silica gel column, eluting with 0→100% EtOAc/hexanes over 24 minutes) gave the title compound (500 mg, yield: 64%).

後処理

  1. customthe ice bath was removed
  2. stirringThe reaction was stirred overnight at r.t. whereupon the excess pyridine
  3. customwas removed under reduced pressure
  4. washThe organic layer was washed successively with 50 ml each of 0.5 N aq. HCl, saturated aqueous sodium bicarbonate, and water
  5. dry with materialThe organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. customPurification
  8. washby column chromatography (ISCO, 80 g silica gel column, eluting with 0→100% EtOAc/hexanes over 24 minutes)

出典と根拠

ORDレコード
ord-478ec7fa01b34893be50e90ece5e8c08
出典データセット
uspto-grants-2015_04
特許番号
US09018381B2

反応ノート

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