Isoxazole, 4-(chloromethyl)-3,5-dimethyl- → 4-[(3,5-Dimethyl-4-isoxazolyl)methoxy]-2,6-difluorobenzenemethanol

HRID 1794112Notes

Reaction equation

HRID 1794112 reaction equation
CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC.[F:19][C:20]1[CH:27]=[C:26]([OH:28])[CH:25]=[C:24]([F:29])[C:21]=1[CH2:22][OH:23].Cl[CH2:31][C:32]1[C:33]([CH3:38])=[N:34][O:35][C:36]=1[CH3:37]>C(#N)C>[CH3:38][C:33]1[C:32]([CH2:31][O:28][C:26]2[CH:27]=[C:20]([F:19])[C:21]([CH2:22][OH:23])=[C:24]([F:29])[CH:25]=2)=[C:36]([CH3:37])[O:35][N:34]=1

Participants

5

Reactant 3

HCID 88246Isoxazole, 4-(chloromethyl)-3,5-dimethyl-HCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amineHCID 222199753,5-Difluoro-4-(hydroxymethyl)phenol

Product 1

HCID 222198794-[(3,5-Dimethyl-4-isoxazolyl)methoxy]-2,6-difluorobenzenemethanolYield 85%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

PS-BEMP (1.5 g, 2 eq) was added to a solution of 2,6-difluoro-4-hydroxybenzyl alcohol (400 mg, 1.5 eq) in acetonitrile (4 mL) and the mixture was shaken for 5 min. 4-(Chloromethyl)-3,5-dimethylisoxazole (210 uL, 1.67 mmol) was added and the resultant mixture was shaken at ambient temperature for 16 h. The mixture was filtered, the resin washed with dichloromethane (4×4 mL) and evaporated to afford the desired product (380 mg, 85%) as a white solid: NMR δH(400 MHz; d6-DMSO) 2.20 (3H, s), 2.40 (3H, s), 4.42 (2H, d, J 5.5 Hz), 5.95 (2H, s), 5.08 (1H, t, J 5.5 Hz) and 6.76–6.83 (2H, m); HPLC (XTERRA, 50/80, 220 nm) 94.5% (1.03 min).

Workup

  1. filtrationThe mixture was filtered
  2. washthe resin washed with dichloromethane (4×4 mL)
  3. customevaporated

Sources & evidence

ORD record
ord-0db57d5e1870437a82e14fbb82f0b79d
Source dataset
uspto-grants-2006_04
Patent number
US07022707B2

Reaction notes

Loading…