Triphenylphosphine → 5-(3-((4-Acetyl-3-hydroxy-2-methylphenoxy)methyl)phenylthio)nicotinonitrile

HRID 2267056Notes

Reaction equation

HRID 2267056 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[OH:34][CH2:35][C:36]1[CH:37]=[C:38]([S:42][C:43]2[CH:44]=[N:45][CH:46]=[C:47]([CH:50]=2)[C:48]#[N:49])[CH:39]=[CH:40][CH:41]=1.[OH:51][C:52]1[C:57]([CH3:58])=[C:56](O)[CH:55]=[CH:54][C:53]=1[C:60](=[O:62])[CH3:61]>C1COCC1>[C:60]([C:53]1[CH:54]=[CH:55][C:56]([O:34][CH2:35][C:36]2[CH:37]=[C:38]([S:42][C:43]3[CH:44]=[N:45][CH:46]=[C:47]([CH:50]=3)[C:48]#[N:49])[CH:39]=[CH:40][CH:41]=2)=[C:57]([CH3:58])[C:52]=1[OH:51])(=[O:62])[CH3:61]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5921391-(2,4-Dihydroxy-3-methylphenyl)ethan-1-oneHCID 5363146Diisopropyl azodicarboxylateHCID 685380695-(3-(Hydroxymethyl)phenylthio)nicotinonitrile

Product 1

HCID 595995825-(3-((4-Acetyl-3-hydroxy-2-methylphenoxy)methyl)phenylthio)nicotinonitrileYield 50.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add triphenylphosphine (5.24 g, 20.0 mmol) and diisopropylazodicarboxylate (4.04 g, 20.0 mmol) to a solution of 5-(3-(hydroxymethyl)phenylthio)nicotinonitrile (4.84 g, 20.0 mmol) and 1-(2,4-dihydroxy-3-methylphenyl)ethanone (3.32 g, 20.0 mmol) in THF (100 mL). Stir the reaction for 24 h. Quench the reaction with water and extract with EtOAc. Dry, filter and concentrate. Purify the residue by flash chromatography on silica gel eluting with a mixture of EtOAc and hexanes (15:85 to 20:80) to give an off-white solid. Recrystallize the solid from a mixture of EtOAc and hexanes to afford the title compound (3.94 g, 50%): 1H NMR (CDCl3) δ 2.14 (s, 3H), 2.57 (s, 3H), 5.18 (s, 2H), 6.44 (d, J=9.0 Hz, 1H), 7.46-7.49 (m, 3H), 7.52 (s, 1H), 7.59 (d, J=9.0 Hz, 1H), 7.62-7.63 (m, 1H), 8.63-8.64 (m, 2H), 12.78 (s, 1H).

Workup

  1. customthe reaction for 24 h
  2. customQuench
  3. customthe reaction with water
  4. extractionextract with EtOAc
  5. customDry
  6. filtrationfilter
  7. concentrationconcentrate
  8. customPurify the residue by flash chromatography on silica gel eluting
  9. additionwith a mixture of EtOAc and hexanes (15:85 to 20:80)
  10. customto give an off-white solid
  11. customRecrystallize the solid
  12. additionfrom a mixture of EtOAc and hexanes

Sources & evidence

ORD record
ord-bcd7229c1bcf42b98d08a445d65c2a01
Source dataset
uspto-grants-2010_12
Patent number
US07858646B2

Reaction notes

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