Thionyl Chloride → 4-(Chloromethyl)-3-(2,6-dichlorophenyl)-5-isopropylisoxazole

HRID 2423387Notes

Reaction equation

HRID 2423387 reaction equation
S(Cl)([Cl:3])=O.N1C2C=CC=CC=2N=N1.[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[C:16]=1[C:22]1[C:26]([CH2:27]O)=[C:25]([CH:29]([CH3:31])[CH3:30])[O:24][N:23]=1>ClCCl>[Cl:3][CH2:27][C:26]1[C:22]([C:16]2[C:15]([Cl:14])=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:21])=[N:23][O:24][C:25]=1[CH:29]([CH3:31])[CH3:30]

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 10850745(3-(2,6-Dichlorophenyl)-5-isopropylisoxazol-4-yl)methanolHCID 178418385HCID 178418385, compound

Product 1

HCID 592648754-(Chloromethyl)-3-(2,6-dichlorophenyl)-5-isopropylisoxazoleYield 104.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Thionyl chloride (123 mL, 202 g, 1.7 mol) was added dropwise during 30 min to a stirred suspension of benzotriazole (202 g, 1.7 mol) in dichloromethane (550 mL) at room temperature under N2. The resulting yellow solution was transferred to an addition funnel and added dropwise during 1 hour to a stirred solution of [3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methanol (372 g, 1.3 mol, Maloney, P. R., et al., 2000 J. Med. Chem. 43:2971-2974) in dichloromethane (975 mL). The reaction temperature gradually rose to a maximum of 28° C. After 1 hr the resulting suspension was filtered to remove the benzotriazole hydrochloride. The filtrate was washed with water (2×1 L), with 1 N NaOH (1 L), with water (1 L), dried over anhydrous Na2SO4, filtered and concentrated to yield 4-(chloromethyl)-3-(2,6-dichlorophenyl)-5-(1-methylethyl)isoxazole as a pale yellow oil (413 g, 80%). 1H NMR (400 MHz, DMSO-d6): 7.64 (m, 3H), 4.47 (s, 2H), 3.45 (m, 1H), 1.31 (d, J=7 Hz, 6H). ES-LCMS m/z 305 (M+H)+.

Workup

  1. customThe resulting yellow solution was transferred to an addition funnel
  2. customgradually rose to a maximum of 28° C
  3. filtrationAfter 1 hr the resulting suspension was filtered
  4. customto remove the benzotriazole hydrochloride
  5. washThe filtrate was washed with water (2×1 L), with 1 N NaOH (1 L), with water (1 L)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-8261ba995d23496ea7b4a369b0e4c006
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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