Toluene → 2-(2-Chloropyrimidin-4-yl)propan-2-ol

HRID 410429Notes

Reaction equation

HRID 410429 reaction equation
C1(C)C=CC=CC=1.C[Mg]Cl.[CH3:11][C:12]([OH:15])([CH3:14])[CH3:13].[Cl:16][C:17]1[N:22]=C(C(OC)=O)[CH:20]=[CH:19][N:18]=1>C1COCC1.CCOC(C)=O>[Cl:16][C:17]1[N:22]=[C:11]([C:12]([OH:15])([CH3:14])[CH3:13])[CH:20]=[CH:19][N:18]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 6386tert-ButanolHCID 43811076Methyl 2-chloropyrimidine-4-carboxylateHCID 178418332HCID 178418332, compound

Product 1

HCID 772310672-(2-Chloropyrimidin-4-yl)propan-2-olYield 71%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of THF (0.25 mL) and toluene (1 mL) at −20° C. under a nitrogen atmosphere was added methyl magnesium chloride (3.0 M in THF, 1 mL, 2.90 mmol) followed by t-BuOH (0.050 mL in 0.750 mL THF, 0.579 mmol) and left to stir for 30 min at 0° C. The solution was cooled back down to −20° C. and methyl 2-chloropyrimidine-4-carboxylate (100 mg, 0.58 mmol) in THF (1 mL) was added. The solution was warmed to room temperature and stirred for an additional 30 min. The solution was diluted with EtOAc, washed with brine, dried with MgSO4, filtered, and concentrated to dryness to afford 2-(2-chloropyrimidin-4-yl)propan-2-ol (71 mg, 0.41 mmol, 71% yield. MS ESI: [M+H]+ m/z 173.1. 1H NMR (500 MHz, CDCl3) δ 8.60 (dd, J=1.8, 5.1, 1H), 7.44 (d, J=5.1 1H), 1.56 (d, J=1.8, 6H).

Workup

  1. waitleft
  2. additionwas added
  3. temperatureThe solution was warmed to room temperature
  4. stirringstirred for an additional 30 min
  5. washwashed with brine
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-169341009b0d4ef5aa7b6e82ac616358
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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