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 650737Notes

Reaction equation

HRID 650737 reaction equation
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

Participants

4

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
50 °C

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-9198737def014c9181ce2d9b43c5c3ec
Source dataset
uspto-grants-2001_08
Patent number
US06274735B1

Reaction notes

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