Tributylphosphine → 4-(benzyloxy)-8-methoxy-3-methyl-2-{[3-(tetrahydro-2H-pyran-4-ylmethoxy)phenoxy]methyl}quinoline

HRID 384474Notes

Reaction equation

HRID 384474 reaction equation
[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[C:14]([O:19][CH3:20])[CH:15]=[CH:16][CH:17]=2)[N:12]=[C:11]([CH2:21][OH:22])[C:10]=1[CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:24]1[CH2:29][CH2:28][CH:27]([CH2:30][O:31][C:32]2[CH:33]=[C:34](O)[CH:35]=[CH:36][CH:37]=2)[CH2:26][CH2:25]1.C1CCN(C(/N=N/C(N2CCCCC2)=O)=O)CC1.C(P(CCCC)CCCC)CCC>C1COCC1.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[C:14]([O:19][CH3:20])[CH:15]=[CH:16][CH:17]=2)[N:12]=[C:11]([CH2:21][O:22][C:36]2[CH:35]=[CH:34][CH:33]=[C:32]([O:31][CH2:30][CH:27]3[CH2:26][CH2:25][O:24][CH2:29][CH2:28]3)[CH:37]=2)[C:10]=1[CH3:23])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 13831Tributylphosphine2×HCID 5702657diazenedicarboxylic acid bis(N,N-piperidide)HCID 59526840[4-(Benzyloxy)-8-methoxy-3-methylquinolin-2-yl]methanolHCID 595270023-[(Oxan-4-yl)methoxy]phenol

Product 1

HCID 595271314-(benzyloxy)-8-methoxy-3-methyl-2-{[3-(tetrahydro-2H-pyran-4-ylmethoxy)phenoxy]methyl}quinolineYield 84.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of [4-(benzyloxy)-8-methoxy-3-methylquinolin-2-yl]methanol (250 mg) in THF (10 mL) were added 3-(tetrahydro-2H-pyran-4-ylmethoxy)phenol (185 mg) and 1,1-(azodicarbonyl)dipiperidine (245 mg), followed by dropwise addition of tributylphosphine (0.24 mL) at room temperature and stirring. After 1 hour, tributyl phosphine (0.24 mL) was added thereto, followed by stirring for 12 hours. Ethyl acetate was added to the reaction mixture, and then insolubles were removed by filtration. The filtrate was concentrated under reduced pressure, and then the residue was purified by silica gel column chromatography twice (eluent for the first round: hexane/ethyl acetate=80/20˜67/33˜60/40, eluent for the second round: chloroform˜chloroform/methanol=95/5), and also by thin layer silica gel chromatography (developer: chloroform/methanol=95/5) to obtain 4-(benzyloxy)-8-methoxy-3-methyl-2-{[3-(tetrahydro-2H-pyran-4-ylmethoxy)phenoxy]methyl}quinoline (340 mg).

Workup

  1. stirringby stirring for 12 hours
  2. custominsolubles were removed by filtration
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customthe residue was purified by silica gel column chromatography twice (eluent for the first round: hexane/ethyl acetate=80/20˜67/33˜60/40, eluent for the second round: chloroform˜chloroform/methanol=95/5), and also by thin layer silica gel chromatography (developer: chloroform/methanol=95/5)

Sources & evidence

ORD record
ord-9c11ebaf09d14182b9d690e72ce12321
Source dataset
uspto-grants-2013_02
Patent number
US08367702B2

Reaction notes

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