Hydrochloric Acid → HCID 86602706, compound

HRID 1375052Notes

Reaction equation

HRID 1375052 reaction equation
CS([Cl:5])(=O)=O.[F:6][C:7]([F:57])([F:56])[C:8]1[CH:9]=[C:10]([CH:49]=[C:50]([C:52]([F:55])([F:54])[F:53])[CH:51]=1)[C:11]([N:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][N:21]2[CH2:26][CH2:25][O:24][C@H:23]([CH2:27][O:28][CH3:29])[CH2:22]2)[CH2:15][C@H:14]1[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([C:37](O)([CH3:39])[CH3:38])=[C:33]([O:41][Si](C(C)(C)C)(C)C)[CH:32]=1)=[O:12].C(N(CC)CC)C.[ClH:65]>ClCCl.C(OCC)(=O)C.[OH-].[OH-].[Pd+2].CO>[ClH:5].[ClH:65].[F:55][C:52]([F:53])([F:54])[C:50]1[CH:49]=[C:10]([CH:9]=[C:8]([C:7]([F:6])([F:56])[F:57])[CH:51]=1)[C:11]([N:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][N:21]2[CH2:26][CH2:25][O:24][C@H:23]([CH2:27][O:28][CH3:29])[CH2:22]2)[CH2:15][C@H:14]1[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([CH:37]([CH3:39])[CH3:38])=[C:33]([OH:41])[CH:32]=1)=[O:12]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 57193823HCID 57193823, compound

Product 1

HCID 86602706HCID 86602706, compound

Reagents, catalysts & solvents 4

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methanesulfonyl chloride (0.115 ml) was added to an ice-cooled solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-[3-(tert-butyldimethylsilyloxy)-4-(1-hydroxy-1-methylethyl)benzyl]-4-[2-[(2S)-2-(methoxymethyl)morpholino]-ethyl]piperazine (0.76 g) and triethylamine (0.35 ml) in dichloromethane (9 ml). After being stirred at the same temperature for 2 hours, the mixture was washed with water. The organic layer was separated, washed with brine, dried over magnesium sulfate and evaporated under reduced pressure to give a mixture of the mesylated and unmesylated compound. The mixture was dissolved into methanol without further purification and the solution was hydrogenated over 20% palladium hydroxide-charcoal (0.1 g) at room temperature at 3 atmosphere for 5 hours. The reaction mixture was filtered through Celite® and washed with methanol. The filtrate and washing were combined and evaporated under reduced pressure. The resulting syrup was dissolved in tetrahydrofuran (6.5 ml) and thereto tetrabutylammonium fluoride (1M solution of tetrahydrofuran, 0.1 ml) was added below 10° C. After stirring at room temperature, the mixture was evaporated under reduced pressure and the residue was purified by column chromatography using a mixed solvent of dichloromethane and methanol (40:1) to give an oil. The oil was treated with 4N hydrogen chloride in ethyl acetate to give a powder of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-[3-hydroxy-4-(1-methylethyl)benzyl]-4-[2-[(2S)-2-(methoxymethyl)morpholino]-ethyl]piperazine dihydrochloride (150 mg).

Workup

  1. washthe mixture was washed with water
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated under reduced pressure
  6. customto give
  7. additiona mixture of the
  8. filtrationThe reaction mixture was filtered through Celite®
  9. washwashed with methanol
  10. washThe filtrate and washing
  11. customevaporated under reduced pressure
  12. dissolutionThe resulting syrup was dissolved in tetrahydrofuran (6.5 ml)
  13. additiontetrabutylammonium fluoride (1M solution of tetrahydrofuran, 0.1 ml) was added below 10° C
  14. stirringAfter stirring at room temperature
  15. customthe mixture was evaporated under reduced pressure
  16. customthe residue was purified by column chromatography
  17. customto give an oil

Sources & evidence

ORD record
ord-2bff53b2cffc4f919041b7fca77281a8
Source dataset
uspto-grants-2007_01
Patent number
US07166598B2

Reaction notes

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