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

HRID 2423485Notes

Reaction equation

HRID 2423485 reaction equation
[CH:1]1([O:6][CH2:7][C:8]2[C:12]([CH2:13][OH:14])=[C:11]([CH:15]([CH3:17])[CH3:16])[O:10][N:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.O[C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:26]=[C:27]3[C:32](=[CH:33][CH:34]=2)[N:31]=[C:30]([C:35]([O:37][CH3:38])=[O:36])[CH:29]=[CH:28]3)=[CH:21][CH:20]=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([O:6][CH2:7][C:8]2[C:12]([CH2:13][O:14][C:19]3[CH:20]=[CH:21][C:22]([C:25]4[CH:26]=[C:27]5[C:32](=[CH:33][CH:34]=4)[N:31]=[C:30]([C:35]([O:37][CH3:38])=[O:36])[CH:29]=[CH:28]5)=[CH:23][CH:24]=3)=[C:11]([CH:15]([CH3:17])[CH3:16])[O:10][N:9]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 59321540Methyl 6-(4-hydroxyphenyl)-2-quinolinecarboxylateHCID 59321541[3-[(Cyclopentyloxy)methyl]-5-(1-methylethyl)-4-isoxazolyl]methanol

Product 1

HCID 59321471Methyl 6-[4-({[3-[(cyclopentyloxy)methyl]-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylateYield 11%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of [3-[(cyclopentyloxy)methyl]-5-(1-methylethyl)-4-isoxazolyl]methanol (50 mg, 0.21 mmol) in dichloromethane (2.1 mL) was added to a mixture of methyl 6-(4-hydroxyphenyl)-2-quinolinecarboxylate (57 mg, 0.21 mmol) and triphenyl phosphine (82 mg, 0.31 mmol) in a microwave reaction tube. Diisopropyl azodicarboxylate (60 μL, 0.31 mmol) was added before the tube was sealed and heated for 20 minutes at 100° C. The mixture was concentrated and the residue was purified by chromatography (silica gel, hexane to 2:3 ethyl acetate:hexanes). Fractions containing the product were combined and concentrated. The residue was purified by chromatography (silica gel, 10:9:1 hexanes:dichloromethane:ethyl acetate) to provide methyl 6-[4-({[3-[(cyclopentyloxy)methyl]-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate (11 mg, 11% as 0.10 ethyl acetate). 1H NMR (400 MHz, CDCl3): δ 8.37-8.32 (m, 2H), 8.22 (d, J=9 Hz, 1H), 8.05-8.00 (m, 2H), 7.69 (d, J=9 Hz, 2H), 7.08 (d, J=9 Hz, 2H), 4.99 (s, 2H), 4.58 (s, 2H), 4.09 (s, 3H), 3.99-3.97 (m, 1H), 3.27 (septet, J=7 Hz, 1H), 1.70-1.59 (m, 6H), 1.49-1.46 (m, 2H), 1.33 (d, J=7 Hz, 6H).

Workup

  1. customwas sealed
  2. concentrationThe mixture was concentrated
  3. customthe residue was purified by chromatography (silica gel, hexane to 2:3 ethyl acetate:hexanes)
  4. additionFractions containing the product
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography (silica gel, 10:9:1 hexanes:dichloromethane:ethyl acetate)

Sources & evidence

ORD record
ord-4b2d260e27cf4155aa434bfd51ef5bfc
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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