Hydrochloric Acid → 6-[(1S)-1,3-Dihydroxy-1-[1-(triphenylmethyl)-1H-imidazol-4-yl]propyl]-N-methyl-2-naphthalenecarboxamide

HRID 1444946Notes

Reaction equation

HRID 1444946 reaction equation
[OH:1][C@@:2]([C:33]1[CH:42]=[CH:41][C:40]2[C:35](=[CH:36][CH:37]=[C:38]([C:43]([NH:45][CH3:46])=[O:44])[CH:39]=2)[CH:34]=1)([C:9]1[N:10]=[CH:11][N:12]([C:14]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:13]=1)[CH2:3][C:4](OCC)=[O:5].[BH4-].[Na+].[Cl-].[Ca+2].[Cl-].Cl>C(OCC)(=O)C.O.C(O)C.C1COCC1>[OH:1][C@@:2]([C:33]1[CH:34]=[C:35]2[C:40](=[CH:41][CH:42]=1)[CH:39]=[C:38]([C:43]([NH:45][CH3:46])=[O:44])[CH:37]=[CH:36]2)([C:9]1[N:10]=[CH:11][N:12]([C:14]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:13]=1)[CH2:3][CH2:4][OH:5]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 5284359Calcium ChlorideHCID 57465807Ethyl (3S)-3-hydroxy-3-(6-((methylamino)carbonyl))-2-naphthyl)-3-(1-trityl-1H-imidazil-4-yl) propanoate

Product 1

HCID 574658086-[(1S)-1,3-Dihydroxy-1-[1-(triphenylmethyl)-1H-imidazol-4-yl]propyl]-N-methyl-2-naphthalenecarboxamideYield 89.3%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

13 mL of THF was added to 1.3 g (2.13 mmol) of ethyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate, and 0.645 g (17.1 mmol, 8 eq) of sodium borohydride was added. 0.95 g (8.53 mmol, 4 eq) of calcium chloride was added at 2° C. 13 mL of ethanol was added dropwise at 2° C. over 15 minutes. The mixture was stirred at 3˜4° C. for 30 minutes, and at 40˜43° C. for 4 hours. 56 mL of water was added dropwise. 17.1 mL of 1N hydrochloric acid was added dropwise, followed by dilution with 40 mL of ethyl acetate. Then, the layers were separated. The aqueous layer was re-extracted with 20 mL of ethyl acetate. The organic layers were combined, and washed with 20 mL of an aqueous saturated sodium chloride solution two times. After concentration under reduced pressure, IPE was added to the concentration residue, crystals were loosened, filtered and washed with IPE. Vacuum drying (50° C.) to a constant weight afforded 1.08 g of 6-[(1S)-1,3-dihydroxy-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (yield 89%, enantiomer excess 92.0% ee).

Workup

  1. additionwas added
  2. waitat 40˜43° C. for 4 hours
  3. customThen, the layers were separated
  4. extractionThe aqueous layer was re-extracted with 20 mL of ethyl acetate
  5. washwashed with 20 mL of an aqueous saturated sodium chloride solution two times
  6. concentrationAfter concentration under reduced pressure, IPE
  7. additionwas added to the concentration residue, crystals
  8. filtrationfiltered
  9. washwashed with IPE
  10. customVacuum drying (50° C.) to a constant weight

Sources & evidence

ORD record
ord-3650db1cf6ed43b28226e6190dd5a21c
Source dataset
uspto-grants-2010_02
Patent number
US07662974B2

Reaction notes

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