Potassium Carbonate → (S)-1-(5-bromopyrimidin-2-yl)ethanol

HRID 1399984Notes

Reaction equation

HRID 1399984 reaction equation
[Br:1]/[C:2](=[CH:5]\N(C)C)/[CH:3]=O.C(=O)([O-])[O-].[K+].[K+].Cl.[OH:16][C:17]([CH3:22])(C)[C:18]([NH2:20])=[NH:19]>C(O)C>[Br:1][C:2]1[CH:3]=[N:19][C:18]([C@@H:17]([OH:16])[CH3:22])=[N:20][CH:5]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 215914792-Bromo-3-(dimethylamino)acroleinHCID 426142842-Hydroxy-2-methylpropanimidamide hydrochloride

Product 1

HCID 86696897(S)-1-(5-bromopyrimidin-2-yl)ethanolYield 16%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
85 °C

Procedure

(Z)-2-bromo-3-(dimethylamino)prop-2-enal (11.5 g), potassium carbonate (13.4 g), ethanol (200 mL) and 2-hydroxy-2-methyl-propanamidine hydrochloride (12.1 g) were placed in a flask and the mixture heated at 85° C. overnight. The reaction mixture was cooled and the mixture filtered, washed with ethanol and the combined filtrates concentrated in vacuo with silica gel. This residue was purified by chromatography on silica, eluting with 0-50% ethyl acetate in heptane to give (1S)-1-(5-bromopyrimidin-2-yl)ethanol as a white solid (2.1 g, 16%). 1H NMR (CDCl3) δ 8.83 (s, 2H), 4.98 (m, 1H), 3.8 (m, 1H), 1.6 (d, J=6.6 Hz, 3H). Chiral HPLC: Column. Chirapak IC, 0.46 cm×25 cm; 20 min isocratic gradent; 5:95 EtOH:n-hexane+0.1% diethylamine) retention time=14.08 min. (racemic mixture: ˜14.5 min: S isomer; ˜17.5 min: R isomer).

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationthe mixture filtered
  3. washwashed with ethanol
  4. concentrationthe combined filtrates concentrated in vacuo with silica gel
  5. customThis residue was purified by chromatography on silica
  6. washeluting with 0-50% ethyl acetate in heptane

Sources & evidence

ORD record
ord-eedb5706b2a841bf8e35ee149a0c0812
Source dataset
uspto-grants-2014_12
Patent number
US08906902B2

Reaction notes

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