(S)-mandelic acid → 3-[4-(2-(Cyclopropylmethoxy)ethyl)phenoxy]-2-hydroxypropylamine

HRID 1906678Notes

Reaction equation

HRID 1906678 reaction equation
[CH:1]1([CH2:4][O:5][CH2:6][CH2:7][C:8]2[CH:19]=[CH:18][C:11]([O:12][CH2:13][CH:14]([OH:17])[CH2:15][NH2:16])=[CH:10][CH:9]=2)[CH2:3][CH2:2]1.[C:20]([OH:30])(=[O:29])[C@H:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[OH:22]>O.CO>[C:20]([O-:30])(=[O:29])[CH:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[OH:22].[CH:1]1([CH2:4][O:5][CH2:6][CH2:7][C:8]2[CH:9]=[CH:10][C:11]([O:12][CH2:13][CH:14]([OH:17])[CH2:15][NH2:16])=[CH:18][CH:19]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 2

HCID 439616(S)-mandelic acidHCID 140252973-[4-(2-(Cyclopropylmethoxy)ethyl)phenoxy]-2-hydroxypropylamine

Product 2

HCID 3839223Mandelate ionHCID 140252973-[4-(2-(Cyclopropylmethoxy)ethyl)phenoxy]-2-hydroxypropylamineYield 20.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

(±)-3-[4-(2-(Cyclopropylmethoxy)ethyl)phenoxy]-2-hydroxypropylamine (25 g) was dissolved in hot water (200 ml) and methanol (50 ml). To this solution was added, with vigorous stirring, a solution of L-(+)-mandelic acid (14.35 g) in hot water (200 ml). The mixture was stirred for five minutes, cooled and seeded to give crystals. These were collected and recrystallised three times from hot water to afford a mandelate salt of 3-[4-(2-(cyclopropylmethoxy)ethyl)phenoxy]-2-hydroxypropylamine (5.04 g). To part of this compound (4.54 g) in chloroform (75 ml) was added 15% sodium carbonate solution (75 ml) and the two phase mixture was vigorously stirred at room temperature for one hour. The two layers were separated, the aqueous layer washed with chloroform (3×25 ml) and the organic layer and chloroform washings were combined, dried and evaporated under reduced pressure to give a residue (2.81 g). This residue was dissolved in hot acetonitrile (25 ml), filtered, evaporated to low volume and cooled to afford (-)-3-[4-(2-(cyclopropylmethoxy)ethyl)phenoxy]-2-hydroxypropylamine (2.05 g), [α]D25 =-17.77° [concentration 1.1% in ethanol:water:concentrated HCl (17:2:1)]: nuclear magnetic resonance spectrum consistent with racemic material; identical by chromatography.

Workup

  1. additionTo this solution was added, with vigorous stirring
  2. temperaturecooled
  3. customto give crystals
  4. customThese were collected
  5. customrecrystallised three times from hot water

Sources & evidence

ORD record
ord-9676132538b742bf918f05632d6293ae
Source dataset
uspto-grants-1987_03
Patent number
US04652563

Reaction notes

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