Tributylphosphine → Methyl [(3S)-6-({3'-fluoro-2',6'-dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetate

HRID 416188Notes

Reaction equation

HRID 416188 reaction equation
[OH:1][C:2]1[CH:15]=[CH:14][C:5]2[C@H:6]([CH2:9][C:10]([O:12][CH3:13])=[O:11])[CH2:7][O:8][C:4]=2[CH:3]=1.[F:16][C:17]1[C:18]([CH3:40])=[C:19]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38]O)[CH:33]=2)[C:20]([CH3:31])=[CH:21][C:22]=1[O:23][CH2:24][CH2:25][CH2:26][S:27]([CH3:30])(=[O:29])=[O:28].C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>CCCCCC.O1CCCC1.C1(C)C=CC=CC=1>[CH3:13][O:12][C:10](=[O:11])[CH2:9][C@H:6]1[C:5]2[CH:14]=[CH:15][C:2]([O:1][CH2:38][C:34]3[CH:33]=[C:32]([C:19]4[C:20]([CH3:31])=[CH:21][C:22]([O:23][CH2:24][CH2:25][CH2:26][S:27]([CH3:30])(=[O:29])=[O:28])=[C:17]([F:16])[C:18]=4[CH3:40])[CH:37]=[CH:36][CH:35]=3)=[CH:3][C:4]=2[O:8][CH2:7]1

Participants

8

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 53393313(S)-Methyl 2-(6-hydroxy-2,3-dihydrobenzofuran-3-yl)acetateHCID 59342565{3'-Fluoro-2',6'-dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methanol

Product 1

HCID 59342579Methyl [(3S)-6-({3'-fluoro-2',6'-dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetateYield 77%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

A solution of methyl [(3S)-6-hydroxy-2,3-dihydro-1-benzofuran-3-yl]acetate (0.729 g, 3.50 mmol), {3′-fluoro-2′,6′-dimethyl-4′-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methanol (1.28 g, 3.50 mmol) and tributylphosphine (1.13 g, 5.60 mmol) in a mixed solvent of toluene (45 mL) and tetrahydrofuran (5 mL) was stirred, 1,1′-(azodicarbonyl)dipiperidine (1.41 g, 5.60 mmol) was added, and the mixture was stirred at room temperature for 4 hr under nitrogen atmosphere. Hexane (50 mL) was added to the reaction mixture, the precipitated insoluble substance was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=40:60-80:20) and basic silica gel column chromatography (ethyl acetate:hexane=40:60-100:0), and the obtained crystals were recrystallized from heptane-ethyl acetate to give the title compound (1.50 g, yield 77%) as colorless crystals.

Workup

  1. filtrationthe precipitated insoluble substance was filtered off
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=40:60-80:20) and basic silica gel column chromatography (ethyl acetate:hexane=40:60-100:0)
  4. customthe obtained crystals were recrystallized from heptane-ethyl acetate

Sources & evidence

ORD record
ord-052c6b8f0b7f433f98074e5123357150
Source dataset
uspto-grants-2012_01
Patent number
US08088821B2

Reaction notes

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