(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 515855Notes

Reaction equation

HRID 515855 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 minutes. 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 hour 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 minutes (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 hour

Sources & evidence

ORD record
ord-4694b9b1dc9b4da393ab84dac5994ffa
Source dataset
uspto-grants-2015_08
Patent number
US09108984B2

Reaction notes

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