Imidazole → HCID 57244277, compound

HRID 1838736Notes

Reaction equation

HRID 1838736 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([O:14][CH2:15][C:16]2[CH:25]=[C:24]([O:26][CH3:27])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=2)[C@@H:11]([C:28]2[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH2:36][CH2:37][O:38][CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=3[O:46][CH3:47])=[CH:30][CH:29]=2)[C@H:10]([CH2:48]O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.CS(Cl)(=O)=O.[NH:62]1[CH:66]=[CH:65][N:64]=[CH:63]1.[H-].[Na+]>O1CCCC1.ClCCl.CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([O:14][CH2:15][C:16]2[CH:25]=[C:24]([O:26][CH3:27])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=2)[C@@H:11]([C:28]2[CH:29]=[CH:30][C:31]([O:34][CH2:35][CH2:36][CH2:37][O:38][CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=3[O:46][CH3:47])=[CH:32][CH:33]=2)[C@H:10]([CH2:48][N:62]2[CH:66]=[CH:65][N:64]=[CH:63]2)[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

9

Reactant 5

HCID 795ImidazoleHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 57261710HCID 57261710, compound

Product 1

HCID 57244277HCID 57244277, compoundYield 88.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1.5 g (2.2 mmol) of (3S,4R,5R)-3-hydroxymethyl-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-5-(4-methoxy-naphthalen-2-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester [Example 13 (h)] in 40 ml of tetrahydrofurane were added 0.9 ml (6.7 mmol) of triethylamine and thereafter dropwise at 0° C. 512 mg (4.5 mmol) of methanesulphonyl chloride. The reaction solution was stirred at room temperature for 2 hours. For the working-up, the reaction solution was diluted with 50 ml of dichloromethane, extracted with 20 ml of saturated sodium hydrogencarbonate solution, dried over sodium sulfate and evaporated under reduced pressure. The solid crude mesylate was dissolved in 30 ml of N,N-dimethylformamide and thereafter added dropwise to a solution beforehand prepared of 456 mg (6.7 mmol) of imidazole and 322 mg (about 6.7 mmol) of sodium hydride dispersion in refined oil (55-65%) in 10 ml of N,N-dimethylformamide. The reaction mixture was stirred at 100° C. for 6 hours and thereafter evaporated under reduced pressure. The residue was taken up in 50 ml of dichloromethane and then extracted with 20 ml of saturated sodium hydrogencarbonate solution. The organic phase was separated and dried over sodium sulfate and subsequently evaporated under reduced pressure. For purification, the crude product was chromatographed on silica gel using a 98:2 mixture of dichloromethane and methanol as the eluent. There were obtained 1.4 g of (3R,4R,5R)-3-imidazol-1-ylmethyl-4-{4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl}-5-(4-methoxy-naphthalen-2-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester as a yellowish foam; MS: 722 (M+H)+.

Workup

  1. customdropwise at 0° C
  2. extractionextracted with 20 ml of saturated sodium hydrogencarbonate solution
  3. dry with materialdried over sodium sulfate
  4. customevaporated under reduced pressure
  5. dissolutionThe solid crude mesylate was dissolved in 30 ml of N,N-dimethylformamide
  6. additionadded dropwise to a solution
  7. stirringThe reaction mixture was stirred at 100° C. for 6 hours
  8. customevaporated under reduced pressure
  9. extractionextracted with 20 ml of saturated sodium hydrogencarbonate solution
  10. customThe organic phase was separated
  11. dry with materialdried over sodium sulfate
  12. customsubsequently evaporated under reduced pressure
  13. customFor purification
  14. customthe crude product was chromatographed on silica gel using
  15. additiona 98:2 mixture of dichloromethane and methanol as the eluent

Sources & evidence

ORD record
ord-9d2b9ebc5dce4ab492b9ee0238369e6b
Source dataset
uspto-grants-2004_01
Patent number
US06673931B2

Reaction notes

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