Acetone → (R)-3-(N-Isopropylamino)-5-methoxychroman

HRID 37681

Reaction equation

HRID 37681 reaction equation
[CH:1]([NH:4][CH:5]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][C:12]=2[O:15][CH3:16])[O:7][CH2:6]1)([CH3:3])[CH3:2].CC1C=CC(C(O[C@H](C(O)=O)[C@H](OC(C2C=CC(C)=CC=2)=O)C(O)=O)=O)=CC=1.C(O)C.CC(C)=O>CCOCC.[OH-].[K+]>[CH:1]([NH:4][C@@H:5]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][C:12]=2[O:15][CH3:16])[O:7][CH2:6]1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 180AcetoneHCID 702EthanolHCID 263211Ditoluoyltartaric acid, (+)-HCID 19028181N-isopropyl-5-methoxychroman-3-amine

Product 1

HCID 10489181(R)-3-(N-Isopropylamino)-5-methoxychromanYield 32%

Reagents, catalysts & solvents 1

HCID 88018273KOH diethyletherSolvent

Conditions

Temperature
20 °C

Procedure

The racemic 3-(N-isopropylamino)-5-methoxychroman (IV; 54 g, 0.224 mol) was mixed with an equimolar amount of (+)-di-1,4-toluoyl-D-tartaric acid (98.6 g, 0.244 mol). The mixture was dissolved in boiling ethanol (170 mL)/acetone (70 mL). The salt started to crystallize in the hot solvent mixture but was not filtered off until the solvent had cooled down to room temperature (20° C.). The salt was then recrystallized nine times from ethanol/acetone (1:5) to give the pure diastereomeric salt. Yield: 35% (54 g) (99% e.e). Mp: 166°-168° C. The free enantiomer as the base (R)-3-(N-isopropylamino)-5-methoxychroman was obtained by the extraction of the salt in ether/KOH (1M). Yield: 32%, 17.5 g, [α]D21 -32° (C=0.1;MeOH) Mp. 285°-286° C. (HCl-salt)

Workup

  1. dissolutionThe mixture was dissolved
  2. customto crystallize in the hot solvent mixture
  3. filtrationwas not filtered off until the solvent
  4. customThe salt was then recrystallized nine times from ethanol/acetone (1:5)
  5. customto give the pure diastereomeric salt

Sources & evidence

ORD record
ord-2fec32fb74c54731a473b95d77984a28
Source dataset
uspto-grants-1995_05
Patent number
US05420151

Linked notes

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