Tributylphosphine → ethyl 3-[2-fluoro-4-({4'-[(4-hydroxytetrahydro-2H-thiopyran-4-yl)methoxy]-2',6'-dimethylbiphenyl-3-yl}methoxy)phenyl]propanoate

HRID 273419Notes

Reaction equation

HRID 273419 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([C:9]2[C:14]([CH3:15])=[CH:13][C:12]([O:16][CH2:17][C:18]3([OH:24])[CH2:23][CH2:22][S:21][CH2:20][CH2:19]3)=[CH:11][C:10]=2[CH3:25])[CH:6]=[CH:7][CH:8]=1.[F:26][C:27]1[CH:32]=[C:31](O)[CH:30]=[CH:29][C:28]=1[CH2:34][CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37].C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1>[F:26][C:27]1[CH:32]=[C:31]([O:1][CH2:2][C:3]2[CH:4]=[C:5]([C:9]3[C:10]([CH3:25])=[CH:11][C:12]([O:16][CH2:17][C:18]4([OH:24])[CH2:23][CH2:22][S:21][CH2:20][CH2:19]4)=[CH:13][C:14]=3[CH3:15])[CH:6]=[CH:7][CH:8]=2)[CH:30]=[CH:29][C:28]=1[CH2:34][CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37]

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 23082888Ethyl 3-(2-fluoro-4-hydroxyphenyl)propanoateHCID 231571864-({[3'-(hydroxymethyl)-2,6-dimethylbiphenyl-4-yl]oxy}methyl)tetrahydro-2H-thiopyran-4-ol

Product 1

HCID 58903182ethyl 3-[2-fluoro-4-({4'-[(4-hydroxytetrahydro-2H-thiopyran-4-yl)methoxy]-2',6'-dimethylbiphenyl-3-yl}methoxy)phenyl]propanoateYield 89.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-({[3′-(hydroxymethyl)-2,6-dimethylbiphenyl-4-yl]oxy}methyl)tetrahydro-2H-thiopyran-4-ol (0.90 g, 2.51 mmol), ethyl 3-(2-fluoro-4-hydroxyphenyl)propanoate (0.56 g, 2.64 mmol) and tributylphosphine (0.86 mL, 3.26 mmol) in tetrahydrofuran (20 mL) was added 1,1′-(azodicarbonyl)dipiperidine (0.85 g, 3.26 mmol) at room temperature with stirring, and the mixture was stirred for 10 hrs. The resulting precipitate was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=2/1) to give the title compound (1.24 g, yield 89%) as a colorless oil.

Workup

  1. stirringthe mixture was stirred for 10 hrs
  2. filtrationThe resulting precipitate was filtered off
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-dba6ff9b567247529f0a60ed7ad4a735
Source dataset
uspto-grants-2008_11
Patent number
US07456218B2

Reaction notes

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