Hydrochloric Acid → 1-[2-[7-[(3R,4R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidin-3-yloxymethyl]-naphthalen-2-yloxy]-ethyl]-4-methyl-piperazine

HRID 650737ノート

反応式

HRID 650737 の反応式
C(OC([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])=[CH:16][CH:15]=2)[C@@H:10]([O:34][CH2:35][C:36]2[CH:45]=[CH:44][C:43]3[C:38](=[CH:39][C:40]([O:46][CH2:47][CH2:48][N:49]4[CH2:54][CH2:53][N:52]([CH3:55])[CH2:51][CH2:50]4)=[CH:41][CH:42]=3)[CH:37]=2)[CH2:9]1)=O)(C)(C)C.Cl>CO>[CH3:33][O:32][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[CH2:25][O:24][CH2:23][CH2:22][CH2:21][O:20][C:17]1[CH:16]=[CH:15][C:14]([C@H:11]2[CH2:12][CH2:13][NH:8][CH2:9][C@@H:10]2[O:34][CH2:35][C:36]2[CH:37]=[C:38]3[C:43]([CH:42]=[CH:41][C:40]([O:46][CH2:47][CH2:48][N:49]4[CH2:50][CH2:51][N:52]([CH3:55])[CH2:53][CH2:54]4)=[CH:39]3)=[CH:44][CH:45]=2)=[CH:19][CH:18]=1

参加物

4

反応物 2

HCID 313Hydrochloric AcidHCID 57227299(3R,4R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-3-[7-[2-(4-methyl-piperazin-1-yl)-ethoxy]-naphthalen-2-ylmethoxy]-piperidine-1-carboxylic acid tert-butylester

生成物 1

HCID 98525821-[2-[7-[(3R,4R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidin-3-yloxymethyl]-naphthalen-2-yloxy]-ethyl]-4-methyl-piperazine

試薬・触媒・溶媒 1

HCID 887Methanol溶媒2 回

反応条件

温度
50 °C

実験手順

A solution of 9.15 g (12.14 mmol) (3R,4R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-3-[7-[2-(4-methyl-piperazin-1-yl)-ethoxy]-naphthalen-2-ylmethoxy]-piperidine-1-carboxylic acid tert-butylester in 250 ml of methanol was treated at room temperature with 36.41 ml of a 2.0 M solution of hydrogen chloride in methanol and the mixture was stirred at 50° C. for 4 hours. Subsequently, the solution was evaporated under reduced pressure and the residue was partitioned between 200 ml of saturated sodium carbonate solution and 150 ml of methylene chloride. The aqueous phase was again extracted twice with 100 ml of methylene chloride; thereafter the organic phases were combined, dried over sodium sulphate and evaporated under reduced pressure. For purification, the crude product was chromatographed on silica gel using a 90:10 mixture of methylene chloride and methanol as the eluent resulting in 5.25 g (66% of theory) of 1-[2-[7-[(3R,4R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidin-3-yloxymethyl]-naphthalen-2-yloxy]-ethyl]-4-methyl-piperazine as an amorphous, colourless solid; MS: 654 (M+H)+.

後処理

  1. customSubsequently, the solution was evaporated under reduced pressure
  2. customthe residue was partitioned between 200 ml of saturated sodium carbonate solution and 150 ml of methylene chloride
  3. extractionThe aqueous phase was again extracted twice with 100 ml of methylene chloride
  4. dry with materialdried over sodium sulphate
  5. customevaporated under reduced pressure
  6. customFor purification
  7. customthe crude product was chromatographed on silica gel using
  8. additiona 90:10 mixture of methylene chloride and methanol as the eluent
  9. customresulting in 5.25 g (66% of theory) of 1-[2-[7-[(3R,4R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidin-3-yloxymethyl]-naphthalen-2-yloxy]-ethyl]-4-methyl-piperazine as an amorphous, colourless solid

出典と根拠

ORDレコード
ord-9198737def014c9181ce2d9b43c5c3ec
出典データセット
uspto-grants-2001_08
特許番号
US06274735B1

反応ノート

読み込み中…