(S)-mandelic acid → (S)-1-(6-Bromo-3-methyl-5-oxo-5H-thiazolo[3,2-a]pyrimidin-7-yl)ethanaminium (S)-2-hydroxy-2-phenylacetate

HRID 1429796Notes

Reaction equation

HRID 1429796 reaction equation
[NH2:1][CH:2]([C:4]1[N:5]=[C:6]2[S:14][CH:13]=[C:12]([CH3:15])[N:7]2[C:8](=[O:11])[C:9]=1[Br:10])[CH3:3].[C:16]([OH:26])(=[O:25])[C@H:17]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[OH:18]>C(O)(C)C>[OH:18][C@@H:17]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:16]([O-:26])=[O:25].[Br:10][C:9]1[C:8](=[O:11])[N:7]2[C:12]([CH3:15])=[CH:13][S:14][C:6]2=[N:5][C:4]=1[C@@H:2]([NH3+:1])[CH3:3]

Participants

4

Reactant 2

HCID 439616(S)-mandelic acidHCID 58111397HCID 58111397, compound

Product 1

HCID 86717602(S)-1-(6-Bromo-3-methyl-5-oxo-5H-thiazolo[3,2-a]pyrimidin-7-yl)ethanaminium (S)-2-hydroxy-2-phenylacetateYield 85%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Conditions

Temperature
72 °C

Procedure

7-(1-Aminoethyl)-6-bromo-3-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one (18.8 g, 65.2 mmol) was dissolved in isopropanol (375 mL) at reflux and then (S)-(+)-mandelic acid (4.84 g, 31.8 mmol) in isopropanol (375 mL) was added dropwise to the amine solution over 35 min. The reaction mixture was allowed to cool to about 72° C. and solid precipitation was observed. The slurry was cooled to room temperature and stirred for 1 hour. The solid product was collected by filtration. The wet cake was washed with isopropanol (100 mL) and dried on the filter under suction for 1 h to give the product (S)-1-(6-bromo-3-methyl-5-oxo-5H-thiazolo[3,2-a]pyrimidin-7-yl)ethanaminium (S)-2-hydroxy-2-phenylacetate (11.9 g) as a white solid. Chiral HPLC analysis was performed on a Lux Cellulose-2, 4.6×250 mm, 5 micron column using 60% ethanol/40% hexanes as the mobile phase at a flow rate of 1 mL/min. The major enantiomer eluted at retention time 11.21 min (99.0 area %). The minor enantiomer eluted at retention time 14.31 min (0.96 area %). The e.e. of the desired product was 98.08%.

Workup

  1. temperatureat reflux
  2. customsolid precipitation
  3. temperatureThe slurry was cooled to room temperature
  4. filtrationThe solid product was collected by filtration
  5. washThe wet cake was washed with isopropanol (100 mL)
  6. customdried on the
  7. filtrationfilter under suction for 1 h

Sources & evidence

ORD record
ord-fbaad0c5dbd74af2a6c40c32914f1335
Source dataset
uspto-grants-2015_01
Patent number
US08940752B2

Reaction notes

Loading…