Hydrochloric Acid → 6-[1,3-dihydroxy-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide

HRID 420216Notes

Reaction equation

HRID 420216 reaction equation
[BH4-].[Na+].[Cl-].[Ca+2].[Cl-].[OH:6][C:7]([C:38]1[CH:47]=[CH:46][C:45]2[C:40](=[CH:41][CH:42]=[C:43]([C:48]([NH:50][CH3:51])=[O:49])[CH:44]=2)[CH:39]=1)([C:14]1[N:15]=[CH:16][N:17]([C:19]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:18]=1)[CH2:8][C:9](OCC)=[O:10].Cl>C1COCC1.O.C(O)C>[OH:6][C:7]([C:38]1[CH:39]=[C:40]2[C:45](=[CH:46][CH:47]=1)[CH:44]=[C:43]([C:48]([NH:50][CH3:51])=[O:49])[CH:42]=[CH:41]2)([C:14]1[N:15]=[CH:16][N:17]([C:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:18]=1)[CH2:8][CH2:9][OH:10]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 5284359Calcium ChlorideHCID 57465806ethyl 3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate

Product 1

HCID 101530586-[1,3-dihydroxy-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamideYield 98%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

360 mL of ethanol and 156 mL of THF were added to 26.7 g (0.71 mol, 8eq) of sodium borohydride. 39.3 g (0.35 mol, 4 eq) of calcium chloride was added at 0° C., and the mixture was stirred at 1˜3° C. for 30 minutes. A solution of 60 g (98 mmol) of ethyl 3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate in 204 mL of THF was added dropwise at 0° C. The mixture was stirred at 0˜10° C. for 30 minutes, and at 20˜26° C. for 5 hours. 360 mL of water, and 1.44 liters of 1N hydrochloric acid were successively added dropwise. The mixture was stirred at 25° C. for 1 hour. Crystals were filtered, and washed with 500 mL of water two times. Vacuum drying (50° C.) to a constant weight afforded 54.5 g of 6-[1,3-dihydroxy-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (yield 87%).

Workup

  1. stirringThe mixture was stirred at 0˜10° C. for 30 minutes
  2. waitat 20˜26° C. for 5 hours
  3. stirringThe mixture was stirred at 25° C. for 1 hour
  4. filtrationCrystals were filtered
  5. washwashed with 500 mL of water two times
  6. customVacuum drying (50° C.) to a constant weight

Sources & evidence

ORD record
ord-27d0f6827c7e4c3799f3dfb5cd280a7d
Source dataset
uspto-grants-2012_01
Patent number
US08093403B2

Reaction notes

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