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

HRID 922726Notes

Reaction equation

HRID 922726 reaction equation
[Cl-].[Ca+2].[Cl-].[BH4-].[Na+].[OH:6][C@@:7]([C:29]1[CH:38]=[CH:37][C:36]2[C:31](=[CH:32][CH:33]=[C:34]([C:39]([NH:41][CH3:42])=[O:40])[CH:35]=2)[CH:30]=1)([C:14]1[N:15]=[CH:16][N:17]([S:19]([C:22]2[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=2)(=[O:21])=[O:20])[CH:18]=1)[CH2:8][C:9](OCC)=[O:10].Cl.[OH-].[Na+]>C(O)C.O1CCCC1.O.C(OCC)(=O)C>[OH:6][C@@:7]([C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[CH:35]=[C:34]([C:39]([NH:41][CH3:42])=[O:40])[CH:33]=[CH:32]2)([C:14]1[N:15]=[CH:16][N:17]([S:19]([C:22]2[CH:23]=[CH:24][C:25]([CH3:26])=[CH:27][CH:28]=2)(=[O:21])=[O:20])[CH:18]=1)[CH2:8][CH2:9][OH:10]

Participants

10

Reactant 5

HCID 313Hydrochloric Acid3×HCID 14798Sodium Hydroxide3×HCID 4311764Sodium borohydrideHCID 5284359Calcium ChlorideHCID 86715405ethyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-tosyl-1H-imidazol-4-yl)propanoate

Product 1

HCID 867154076-[(1S)-1,3-dihydroxy-1-(1-tosyl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamideYield 108.9%

Reagents, catalysts & solvents 4

HCID 702EthanolSolvent3×HCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of anhydrous calcium chloride (1.86 g, 16.3 mmol) in ethanol (32 mL) were added sodium borohydride (1.27 g, 33.6 mmol) and ethanol (5 mL) at −10° C., and the mixture was stirred at −10° C. for 30 min. To the reaction mixture were added dropwise a solution of ethyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-tosyl-1H-imidazol-4-yl)propanoate (2.5 g, 5.6 mmol) in tetrahydrofuran (73 mL)/ethanol (10 mL), and tetrahydrofuran (5 mL) at −10° C. The obtained reaction mixture was stirred at 5° C. for 6 hr, and to the obtained reaction mixture were added dropwise water (100 mL), 1 mol/L hydrochloric acid (40 mL) and ethyl acetate (200 mL) at 10° C. or below, and the mixture was stirred. To the separated organic layer was added 0.2 mol/L hydrochloric acid (14 mL) at 5° C., and the mixture was stirred. The reaction mixture was adjusted to pH 7.5 with 0.5 mol/L aqueous sodium hydroxide solution at 5° C. To the separated organic layer was added again 0.2 mol/L hydrochloric acid (14 mL) at 5° C., and the mixture was stirred. The reaction mixture was adjusted to pH 7.5 with 0.5 mol/L aqueous sodium hydroxide solution at 5° C. To the separated organic layer was added water (10 mL), and the mixture was adjusted to pH 9.5 with 0.5 mol/L aqueous sodium hydroxide solution. To the separated organic layer was added water (120 mL), and the mixture was heated to 60° C., and stirred for 3 hr. The separated organic layer was concentrated at 60° C. under reduced pressure to give 6-[(1S)-1,3-dihydroxy-1-(1-tosyl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (2.9 g, 6.1 mmol).

Workup

  1. customThe obtained reaction mixture
  2. stirringwas stirred at 5° C. for 6 hr
  3. customto the obtained reaction mixture
  4. stirringthe mixture was stirred
  5. stirringthe mixture was stirred
  6. stirringthe mixture was stirred
  7. temperaturethe mixture was heated to 60° C.
  8. stirringstirred for 3 hr
  9. concentrationThe separated organic layer was concentrated at 60° C. under reduced pressure

Sources & evidence

ORD record
ord-2124bc28387144b481941a785778af4e
Source dataset
uspto-grants-2016_03
Patent number
US09278938B2

Reaction notes

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