4,6-Dichloropyrimidine → HCID 86598743, compound

HRID 1192448Notes

Reaction equation

HRID 1192448 reaction equation
[Li+].CC([N-]C(C)C)C.[Cl:9][C:10]1[CH:15]=[C:14]([Cl:16])[N:13]=[CH:12][N:11]=1.[CH:17]1([CH:20]=[O:21])[CH2:19][CH2:18]1>C1COCC1>[CH:17]1([CH:20]([C:15]2[C:10]([Cl:9])=[N:11][CH:12]=[N:13][C:14]=2[Cl:16])[OH:21])[CH2:19][CH2:18]1

Participants

5

Reactant 3

HCID 709434,6-DichloropyrimidineHCID 123114CyclopropanecarboxaldehydeHCID 2724682Lithium diisopropylamide

Product 1

HCID 86598743HCID 86598743, compoundYield 80.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred solution of LDA (9.85 mL, 1.5 M, 15.8 mmol) in THF (20 mL) was added dropwise a solution of 4,6-dichloropyrimidine (2.00 g, 13.4 mmol) in THF (12 mL) at −78° C. After stirring for 1.5 hours, a solution of cyclopropanecarbaldehyde (1.05 g, 15.0 mmol) in THF (10 mL) was added dropwise. The solution was stirred at −78° C. for 1 hour and then quenched by addition of water (10 mL). The reaction mixture was allowed to warm to room temperature and partitioned between EtOAc and water. The organic layer was washed with brine, dried and concentrated. The residue was purified by column chromatography (hexanes/EtOAc, 3:1) to give Cyclopropyl-(4,6-dichloro-pyrimidin-5-yl)-methanol (2.36 g, 80%) as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ 8.70 (s, 1H), 4.56 (m, 1H), 2.63 (d, J=8.0 Hz, 1H), 1.70 (m, 1H), 0.76 (m, 1H), 0.55 (m, 2H).

Workup

  1. stirringThe solution was stirred at −78° C. for 1 hour
  2. customquenched by addition of water (10 mL)
  3. custompartitioned between EtOAc and water
  4. washThe organic layer was washed with brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (hexanes/EtOAc, 3:1)

Sources & evidence

ORD record
ord-3db65c23682741fdb64015c96173f270
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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