Triphenylphosphine → ethyl 3-(4-{[2',6'-dimethyl-4'-(tetrahydro-2H-thiopyran-4-yloxy)biphenyl-3-yl]methoxy}-2-fluorophenyl)propanoate

HRID 273422Notes

Reaction equation

HRID 273422 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:11]=[C:12]([C:16]3[C:21]([CH3:22])=[CH:20][C:19]([OH:23])=[CH:18][C:17]=3[CH3:24])[CH:13]=[CH:14][CH:15]=2)[CH:5]=[CH:4][C:3]=1[CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28].[S:32]1[CH2:37][CH2:36][CH:35](O)[CH2:34][CH2:33]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH3:22][C:21]1[CH:20]=[C:19]([O:23][CH:35]2[CH2:36][CH2:37][S:32][CH2:33][CH2:34]2)[CH:18]=[C:17]([CH3:24])[C:16]=1[C:12]1[CH:13]=[CH:14][CH:15]=[C:10]([CH2:9][O:8][C:6]2[CH:5]=[CH:4][C:3]([CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[C:2]([F:1])[CH:7]=2)[CH:11]=1

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 576296Tetrahydro-2H-thiopyran-4-ol2×HCID 58903128Ethyl 3-{2-fluoro-4-[(4'-hydroxy-2',6'-dimethylbiphenyl-3-yl)methoxy]phenyl}propanoate

Product 1

HCID 58903212ethyl 3-(4-{[2',6'-dimethyl-4'-(tetrahydro-2H-thiopyran-4-yloxy)biphenyl-3-yl]methoxy}-2-fluorophenyl)propanoateYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 3-{2-fluoro-4-[(4′-hydroxy-2′,6′-dimethylbiphenyl-3-yl)methoxy]phenyl}propanoate (0.50 g, 1.18 mmol), tetrahydro-2H-thiopyran-4-ol (0.15 g, 1.30 mmol) and triphenylphosphine (0.31 g, 1.30 mmol) in tetrahydrofuran (10 mL) was added diethyl azodicarboxylate (40% toluene solution, 0.70 mL, 1.53 mmol) at room temperature with stirring. The reaction mixture was stirred at room temperature for 19 hrs., and an equivalent amount of the aforementioned reagents (tetrahydro-2H-thiopyran-4-ol, triphenylphosphine and diethyl azodicarboxylate) were added. The mixture was further stirred at the same temperature for 6 hrs. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=3/1) to give the title compound (0.53 g, yield 91%) as a yellow oil.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 19 hrs
  2. stirringThe mixture was further stirred at the same temperature for 6 hrs
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=3/1)

Sources & evidence

ORD record
ord-ad2800bd3659447dbd57b476f3d4122d
Source dataset
uspto-grants-2008_11
Patent number
US07456218B2

Reaction notes

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