Dimethylformamide → (1-{[(2-Chloro-4-pyrimidinyl)oxy]methyl}cyclobutyl)methanol

HRID 1180773

Reaction equation

HRID 1180773 reaction equation
[OH:1][CH2:2][C:3]1([CH2:7][OH:8])[CH2:6][CH2:5][CH2:4]1.CN(C)C=O.[H-].[Na+].[Cl:16][C:17]1[N:22]=[C:21](Cl)[CH:20]=[CH:19][N:18]=1>O1CCCC1>[Cl:16][C:17]1[N:22]=[C:21]([O:1][CH2:2][C:3]2([CH2:7][OH:8])[CH2:6][CH2:5][CH2:4]2)[CH:20]=[CH:19][N:18]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 775312,4-DichloropyrimidineHCID 4498243Cyclobutane-1,1-diyldimethanol

Product 1

HCID 11413552(1-{[(2-Chloro-4-pyrimidinyl)oxy]methyl}cyclobutyl)methanolYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1.00 g (8.62 mmol) of [1-(hydroxymethyl)cyclobutyl]methanol in 20 ml of (1:1) tetrahydrofuran:dimethylforamide was added a 60% dispersion of 0.413 g (8.62 mmol) of sodium hydride in oil. The reaction was stirred for 15 min and 1.28 g (8.62 mmol) of 2,4-dichloropyrimidine was added. After stirring for 2 h, the reaction was concentrated under vacuum and the residue was purified using silica gel chromatography eluting with ethyl acetate:hexane (4:6) to afford 0.9 g (51%) of (1-{[(2-chloro-4-pyrimidinyl)oxy]methyl}cyclobutyl)methanol as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 8.32 (d, J=6 Hz, 1H), 6.69 (d, J=7 Hz, 1H), 4.51 (s, 2H), 3.67 (s, 2H), 2.35 (br s, 1H), 2.05-1.87 (m, 6H).

Workup

  1. stirringAfter stirring for 2 h
  2. concentrationthe reaction was concentrated under vacuum
  3. customthe residue was purified
  4. washeluting with ethyl acetate:hexane (4:6)

Sources & evidence

ORD record
ord-bf592b61f8064edf8a91628f03421b18
Source dataset
uspto-grants-2007_10
Patent number
US07282512B2

Linked notes

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