4-Hydroxybiphenyl → HCID 18444538, compound

HRID 2266800Notes

Reaction equation

HRID 2266800 reaction equation
C([O:3][C:4](=[O:15])[CH2:5][CH2:6][C:7]1[O:8][C:9]([CH3:14])=[C:10]([CH2:12][OH:13])[CH:11]=1)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:35]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:40]=[CH:39][C:38](O)=[CH:37][CH:36]=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCCC1>[C:35]1([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH:40]=[CH:39][C:38]([O:13][CH2:12][C:10]2[CH:11]=[C:7]([CH2:6][CH2:5][C:4]([OH:3])=[O:15])[O:8][C:9]=2[CH3:14])=[CH:37][CH:36]=1

Participants

6

Reactant 4

HCID 71034-HydroxybiphenylHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 58824208HCID 58824208, compound

Product 1

HCID 18444538HCID 18444538, compoundYield 3.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred, cooled 0° C. solution, in tetrahydrofuran (2.5 mL), a solution of 3-(4-hydroxymethyl-5-methyl-furan-2-yl)-propionic acid ethyl ester (36) (400 mg) in tetrahydrofuran (2.5 mL) was cooled to 0° C. and treated successively with triphenylphosphine (542 mg), biphenyl-4-ol (353 mg) and diisopropylazodicarboxylate (0.41 mL). After stirring for 10 mins at 0° C. the reaction mixture was allowed to warm to room temperature and then stirred for a further 16 hours. The reaction mixture was concentrated in-vacuo then re-dissolved in dichloromethane (15 mL) and treated with triethylamine (1.50 mL) and a scavenger resin PS-TsCl (2.5 g) and the mixture was shaken for 6 hours at room temperature. The reaction mixture was purified by flash chromatography, eluting with a mixture of diethyl ether in petroleum ether (40-60° C.) (7:93 by volume). The purified product (320 mg) was dissolved in methanol/tetrahydrofuran (2:1 by volume) (18 mL), treated with 1.0 M aqueous lithium hydroxide solution (9 mL) and allowed to stir at room temperature for 6 hours. The pH of the reaction mixture was adjusted to between pH4 and pH5 by the addition of 1.0 M hydrochloric acid (˜5.0 mL), then treated with saturated ammonium chloride (100 mL) and extracted with ethyl acetate (2×100 mL). The combined organic extracts were further washed with brine (35 mL), then dried (sodium sulphate) and concentrated in vacuo. A sample of the crude product (50 mg) was purified by HPLC to give compound 37 as white solid (25 mg). LC/MS System C: Rt=5.33 mins, m/z (ES−)=335 (M− for C21H20O4).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for a further 16 hours
  3. concentrationThe reaction mixture was concentrated in-vacuo
  4. dissolutionthen re-dissolved in dichloromethane (15 mL)
  5. additiontreated with triethylamine (1.50 mL)
  6. stirringa scavenger resin PS-TsCl (2.5 g) and the mixture was shaken for 6 hours at room temperature
  7. customThe reaction mixture was purified by flash chromatography
  8. washeluting with a mixture of diethyl ether in petroleum ether (40-60° C.) (7:93 by volume)
  9. dissolutionThe purified product (320 mg) was dissolved in methanol/tetrahydrofuran (2:1 by volume) (18 mL)
  10. additiontreated with 1.0 M aqueous lithium hydroxide solution (9 mL)
  11. stirringto stir at room temperature for 6 hours
  12. additionThe pH of the reaction mixture was adjusted to between pH4 and pH5 by the addition of 1.0 M hydrochloric acid (˜5.0 mL)
  13. additiontreated with saturated ammonium chloride (100 mL)
  14. extractionextracted with ethyl acetate (2×100 mL)
  15. washThe combined organic extracts were further washed with brine (35 mL)
  16. dry with materialdried (sodium sulphate)
  17. concentrationconcentrated in vacuo
  18. customA sample of the crude product (50 mg) was purified by HPLC

Sources & evidence

ORD record
ord-2576745cdb6e4f78b2b791ab667587b4
Source dataset
uspto-grants-2010_12
Patent number
US07858644B2

Reaction notes

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