Trifluoroacetic acid → Methyl 6-[4-({[3-(hydroxymethyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate

HRID 2423459Notes

Reaction equation

HRID 2423459 reaction equation
CC([O:5][CH2:6][C:7]1[C:11]([CH2:12][OH:13])=[C:10]([CH:14]([CH3:16])[CH3:15])[O:9][N:8]=1)(C)C.O[C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:25]=[C:26]3[C:31](=[CH:32][CH:33]=2)[N:30]=[C:29]([C:34]([O:36][CH3:37])=[O:35])[CH:28]=[CH:27]3)=[CH:20][CH:19]=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.FC(F)(F)C(O)=O>ClCCl>[OH:5][CH2:6][C:7]1[C:11]([CH2:12][O:13][C:18]2[CH:19]=[CH:20][C:21]([C:24]3[CH:25]=[C:26]4[C:31](=[CH:32][CH:33]=3)[N:30]=[C:29]([C:34]([O:36][CH3:37])=[O:35])[CH:28]=[CH:27]4)=[CH:22][CH:23]=2)=[C:10]([CH:14]([CH3:15])[CH3:16])[O:9][N:8]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 54776256HCID 54776256, compoundHCID 59321540Methyl 6-(4-hydroxyphenyl)-2-quinolinecarboxylate

Product 1

HCID 59321462Methyl 6-[4-({[3-(hydroxymethyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylateYield 70.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
100 °C

Procedure

To a solution of [3-{[(1,1-dimethylethyl)oxy]methyl}-5-(1-methylethyl)-4-isoxazolyl]methanol (407 mg, 1.79 mmol), methyl 6-(4-hydroxyphenyl)-2-quinolinecarboxylate (500 mg, 1.79 mmol) and triphenylphosphine (517 mg, 1.97 mmol) in dichloromethane (4 mL) was added diisopropyl azodicarboxylate (0.354 mL, 1.97 mmol) dropwise. The solution was heated in a microwave reactor at 100° C. for 10 minutes and then adsorbed onto silica gel and purified by chromatography (silica gel, 0-40% ethyl acetate in hexanes gradient elution) to afford a solid which was dissolved in dichloromethane (114 mL). Trifluoroacetic acid (114 mL, 1.48 mol) was added at a rapid pace. The mixture was stirred for approximately 1.5 hours and then concentrated. The residue was taken up with ethyl acetate and poured into water. Then solid sodium carbonate was added until the pH was between 9 and 10. The layers were separated and the ethyl acetate layer was dried over magnesium sulfate and concentrated. The resulting solid was washed with ether to afford methyl 6-[4-({[3-(hydroxymethyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate (545 mg, 54%). 1H-NMR (400 MHz, DMSO-d6) δ 8.57 (d, J=9 Hz, 1H), 8.33 (s, 1H), 8.18 (s, 2H), 8.12 (d, J=9 Hz, 1H), 7.83 (d, J=9 Hz, 2H), 7.17 (d, J=9 Hz, 2H), 5.46 (br s, 1H), 5.06 (s, 2H), 4.54 (s, 2H), 3.94 (s, 3H), 3.33 (septet, J=7 Hz, 1H), 1.24 (d, J=7 Hz, 6H). LRMS (ESI) m/z 433 (M+H)+.

Workup

  1. custompurified by chromatography (silica gel, 0-40% ethyl acetate in hexanes gradient elution)
  2. customto afford a solid which
  3. concentrationconcentrated
  4. additionpoured into water
  5. additionThen solid sodium carbonate was added until the pH was between 9 and 10
  6. customThe layers were separated
  7. dry with materialthe ethyl acetate layer was dried over magnesium sulfate
  8. concentrationconcentrated
  9. washThe resulting solid was washed with ether

Sources & evidence

ORD record
ord-40330db6cbaf4f5780ae8f63b5788374
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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