Water → (R)-3-(1-(naphthalen-1-yl)ethylamino)-1-(3-(trifluoromethyl)phenyl)propan-1-ol hydrochloride

HRID 476311Notes

Reaction equation

HRID 476311 reaction equation
[ClH:1].[C:2]1([C@H:12]([NH:14][CH2:15][CH2:16][C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=2)=[O:18])[CH3:13])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+].[OH-].[Na+].O>CO>[ClH:1].[C:2]1([CH:12]([NH:14][CH2:15][CH2:16][C@H:17]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:26])([F:27])[F:28])[CH:20]=2)[OH:18])[CH3:13])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 46900639(R)-3-(1-(naphthalen-1-yl)ethylamino)-1-(3-(trifluoromethyl)phenyl)propan-1-one hydrochloride

Product 1

HCID 67052600(R)-3-(1-(naphthalen-1-yl)ethylamino)-1-(3-(trifluoromethyl)phenyl)propan-1-ol hydrochlorideYield 91.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

(R)-3-(1-(naphthalen-1-yl)ethylamino)-1-(3-(trifluoromethyl)phenyl)propan-1-one hydrochloride (V) (15.95 g, 39.104 mmol) is suspended in cold methanol (50 ml) at −10° C. and, subsequently, a solution of sodium borohydride (0.75 g, 19.610 mmol), 30% w/w aqueous sodium hydroxide (5.74 g, 43.014 mmol) and water (5 ml) is added slowly in order to keep the internal temperature below 0° C. The reaction mixture is stirred at 0° C. for 0.5 hrs and then quenched by addition of 30% w/w aqueous hydrochloric acid up to pH=1, followed by water (40 ml), and allowed to reach room temperature. The so-formed thick suspension is heated up to 50° C., stirred for 20 minutes and then cooled down to 5° C. The precipitate is filtered, washed with a 9:1 vol/vol water/methanol mixture (10 ml) and dried at 50° C. under vacuum. 14.69 g (35.841 mmol) of high quality (R)-3-(1-(naphthalen-1-yl)ethylamino)-1-(3-(trifluoromethyl)phenyl)propan-1-ol hydrochloride (IXa) are obtained (yield: 91.7%; white powder).

Workup

  1. customthe internal temperature below 0° C
  2. customquenched by addition of 30% w/w aqueous hydrochloric acid up to pH=1
  3. customto reach room temperature
  4. temperatureThe so-formed thick suspension is heated up to 50° C.
  5. stirringstirred for 20 minutes
  6. temperaturecooled down to 5° C
  7. filtrationThe precipitate is filtered
  8. washwashed with a 9:1 vol/vol water/methanol mixture (10 ml)
  9. customdried at 50° C. under vacuum

Sources & evidence

ORD record
ord-5a155910464043a2927182bb3e9c4ca3
Source dataset
uspto-grants-2014_01
Patent number
US08637708B2

Reaction notes

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