Phosphorus oxychloride → HCID 68182134, compound

HRID 1506386Notes

Reaction equation

HRID 1506386 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[CH:8]([NH:14][C:15]([C:17]1[O:21][N:20]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:18]=1[C:28]([F:31])([F:30])[F:29])=O)[CH2:7][CH2:6]2.P(Cl)(Cl)(Cl)=O>ClC(Cl)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]1[O:13][C:15]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[C:18]=3[C:28]([F:29])([F:31])[F:30])=[N:14][C:8]=1[CH2:7][CH2:6]2

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 67169548HCID 67169548, compound

Product 1

HCID 68182134HCID 68182134, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A solution of N-(6-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)-3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxamide (Preparation 43A, 135.6 mg, 0.315 mmol) and phosphorous oxychloride (1.468 mL, 15.75 mmol) in anhydrous dichloroethane (5 mL) was heated under an argon atmosphere at 85° C. for 13 hrs. The solvent and excess phosphorous oxychloride were evaporated off and the residue was purified by Combiflash (12 g silica gel) eluting with 2:8 ethyl acetate-hexane to give the desired 7-methoxy-2-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]oxazole (126 mg, 97% yield) as an oil. 1H NMR (400 MHz, MeOD) δ ppm 7.62-7.66 (2H, m), 7.53-7.60 (3H, m), 7.48 (1H, d, J=8.14 Hz), 6.94 (1H, d, J=2.20 Hz), 6.89-6.93 (1H, m), 3.84 (3H, s), 3.18 (2H, t, J=8.03 Hz), 2.95-3.01 (2H, m).

Workup

  1. customThe solvent and excess phosphorous oxychloride were evaporated off
  2. customthe residue was purified by Combiflash (12 g silica gel)
  3. washeluting with 2:8 ethyl acetate-hexane

Sources & evidence

ORD record
ord-a4681c12d9014f22b046b647d3ea2bb6
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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