Chloromethyl Methyl Ether → HCID 86698434, compound

HRID 527586Notes

Reaction equation

HRID 527586 reaction equation
[OH:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([CH3:13])[C:6](=[O:12])[O:7]2.[H-].[Na+].Cl[CH2:17][O:18][CH3:19]>CN(C)C=O>[CH3:13][C:5]1[C:6](=[O:12])[O:7][C:8]2[C:3]([CH:4]=1)=[C:2]([O:1][CH2:17][O:18][CH3:19])[CH:11]=[CH:10][CH:9]=2

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 20230329HCID 20230329, compound2×

Product 1

HCID 86698434HCID 86698434, compoundYield 77.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-hydroxy-3-methyl-2H-chromen-2-one (Intermediate 112, 2.225 g) in dry N,N-Dimethylformamide (60 ml) cooled to 0° C. was added sodium hydride (60%, 0.532 g, 13.89 mmol) followed by the addition of chloro(methyloxy)methane (1.919 ml, 25.3 mmol). The reaction mixture was warmed to room temperature and stirred for 30 minutes under nitrogen. It was then quenched by the addition of a saturated solution of NH4Cl, the product was extracted with diethyl ether, washed with brine, dried over sodium sulphate, filtered and concentrated under vacuum. The residue obtained was purified by silica gel chromatography (Biotage system, with a gradient from pure cyclohexane to cyclohexane/ethyl acetate 5/1) to give the title compound as a white solid (2.15 g). 1H NMR (400 MHz, CDCl3): δ ppm 7.94 (1H, s), 7.38 (1H, t), 6.93-7.05 (2H, m), 5.33 (2H, s), 3.55 (3H, s), 2.26 (3H, s); UPLC_ipqc: 0.94 min, 221 [M+H]+.

Workup

  1. customIt was then quenched by the addition of a saturated solution of NH4Cl
  2. extractionthe product was extracted with diethyl ether
  3. washwashed with brine
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue obtained
  8. customwas purified by silica gel chromatography (Biotage system

Sources & evidence

ORD record
ord-d5568c738f3e4e99beaf24e2c461057d
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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