4-Fluorophenol → HCID 11538363, compound

HRID 1367697Notes

Reaction equation

HRID 1367697 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[C:9]1([CH:15](O)[CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][N:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:20][CH2:19]2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:15]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][N:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:20][CH2:19]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 97324-FluorophenolHCID 11776Triphenylphosphine2×HCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 14922243HCID 14922243, compound

Product 1

HCID 11538363HCID 11538363, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a stirring solution of THF (10 mL) under N2, 2 equivalents of 4-fluorophenol (1.40 g, 12.4 mmol) was added to a solution of 1-Phenyl-3-(4-phenyl-piperazin-1-yl)-propan-1-ol (20) (1.84 g, 6.22 mmol) and allowed to dissolve. 1.5 equivalents of triphenylphosphine, PPh3, (2.49 g, 9.32 mmol) was then added and dissolved. After the reaction was allowed to equilibrate at a temperature between 10-15° C., 1.5 equivalents of diisopropyl azodicarboxylate, DLAD, (1.85 mL, 9.32 mmol) was added dropwise. The reaction was then allowed to return to room temperature and continued stirring for 48 hours. The solvent was then evaporated under reduced pressure and aspirated under vacuum for an extended period. Purification was performed by Flash Column Chromatography on silica gel by first washing with 500 mL of 10% EtOAc/hexanes and then extracting with 20% EtOAc/hexanes. Analytical thin-layer chromatography showed that the desired product had an Rf value of approximately 0.56 when developed in 30% EtOAc/hexanes. The fractions containing the desired product were combined, and the solvent was removed under reduced pressure. 0.70 g of the product 1a (1.795 mmol, 29%) was obtained as a yellow, clear oil. 1H-NMR (CDCl3): δ 7.29 (7H, m), 6.93 (2H, d, J=7.93 Hz), 6.86 (5H, m), 5.16 (1H, dd, J=5.00, 4.96 Hz), 3.21 (4H, t, J=4.85, 5.10 Hz), 2.60 (6H, m), 2.23 (1H, sextuplet, J=7.26, 6.75, 7.44, 6.91, 7.72 Hz), 2.02 (1H, m). 13C-NMR (CDCl3): δ 155.62, 154.34, 151.28, 141.61, 129.11, 128.63, 127.69, 126.02, 119.72, 117.15, 117.04, 116.09, 115.80, 115.50, 79.34, 54.62, 53.26, 49.15, 35.96. 19F-NMR(CDCl3): δ −123.77.

Workup

  1. dissolutionto dissolve
  2. dissolutiondissolved
  3. customto equilibrate at a temperature between 10-15° C.
  4. customto return to room temperature
  5. customThe solvent was then evaporated under reduced pressure
  6. waitaspirated under vacuum for an extended period
  7. customPurification
  8. washby first washing with 500 mL of 10% EtOAc/hexanes
  9. extractionextracting with 20% EtOAc/hexanes
  10. additionThe fractions containing the desired product
  11. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-efe9d837fd8343299062f51387de14a9
Source dataset
uspto-grants-2011_02
Patent number
US07893261B2

Reaction notes

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