Hydrochloric Acid → HCID 178485275, compound

HRID 922727Notes

Reaction equation

HRID 922727 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(C2C=CC(C)=CC=2)(=O)=O)[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][NH:17][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 178485275HCID 178485275, compoundYield 125%

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 was 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 7° C. for 21 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-(1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (2.3 g, 7.0 mmol).

Workup

  1. customThe obtained reaction mixture
  2. stirringwas stirred at 7° C. for 21 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-9b7c8bae98e54e43b5007e0a0eeb3ec6
Source dataset
uspto-grants-2016_03
Patent number
US09278938B2

Reaction notes

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