Triphenylphosphine → Methyl 6-[4-({[5-cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate

HRID 2423414Notes

Reaction equation

HRID 2423414 reaction equation
[CH:1]1([C:5]2[O:9][N:8]=[C:7]([C:10]3[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=3[Cl:17])[C:6]=2[CH2:18][OH:19])[CH2:4][CH2:3][CH2:2]1.O[C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:28]=[C:29]3[C:34](=[CH:35][CH:36]=2)[N:33]=[C:32]([C:37]([O:39][CH3:40])=[O:38])[CH:31]=[CH:30]3)=[CH:23][CH:22]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[CH:1]1([C:5]2[O:9][N:8]=[C:7]([C:10]3[C:11]([Cl:17])=[CH:12][CH:13]=[CH:14][C:15]=3[Cl:16])[C:6]=2[CH2:18][O:19][C:21]2[CH:22]=[CH:23][C:24]([C:27]3[CH:28]=[C:29]4[C:34](=[CH:35][CH:36]=3)[N:33]=[C:32]([C:37]([O:39][CH3:40])=[O:38])[CH:31]=[CH:30]4)=[CH:25][CH:26]=2)[CH2:2][CH2:3][CH2:4]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 59264868[5-Cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methanolHCID 59321540Methyl 6-(4-hydroxyphenyl)-2-quinolinecarboxylate

Product 1

HCID 59321529Methyl 6-[4-({[5-cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylateYield 35.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of [5-cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methanol (0.12 g, 0.36 mmol), methyl 6-(4-hydroxyphenyl)-2-quinolinecarboxylate (0.10 g, 0.36 mmol) and triphenylphosphine (0.10 mg, 0.39 mmol) in dichloromethane (2.5 mL) was added diisopropyl azodicarboxylate (0.071 mL, 0.39 mmol) dropwise. The solution was heated in a microwave reactor to 90° C. for 10 minutes and the allowed to sit overnight. The solution was adsorbed onto silica gel and purified by chromatography (silica gel, 0-45% ethyl acetate in hexanes gradient elution) to afford methyl 6-[4-({[5-cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate (71 mg, 35%). 1H-NMR (400 MHz, DMSO-d6) δ 8.55 (d, J=9 Hz, 1H), 8.28 (s, 1H), 8.16-8.10 (m, 3H), 7.73 (d, J=9 Hz, 2H), 7.62-7.51 (m, 3H), 6.92 (d, J=9 Hz, 2H), 4.84 (s, 2H), 4.05-3.97 (m, 1H), 3.93 (s, 3H), 2.43-2.31 (m, 4H), 2.14-2.02 (m, 1H), 1.97-1.89 (m, 1H). LRMS (APCI) m/z 559 (M+H)+.

Workup

  1. custompurified by chromatography (silica gel, 0-45% ethyl acetate in hexanes gradient elution)

Sources & evidence

ORD record
ord-b4a528ce662146129b29c36cc31cd7ad
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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