Tributylphosphine → 3-[[4-(4-Acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenyl]-(tetrahydro-pyran-2-yloxy)-methyl]-benzonitrile

HRID 1161027

Reaction equation

HRID 1161027 reaction equation
[OH:1][C:2]1[C:7]([CH2:8][CH2:9][CH3:10])=[C:6]([OH:11])[CH:5]=[CH:4][C:3]=1[C:12](=[O:14])[CH3:13].O[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH:23]([O:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)[C:24]2[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=2)[C:27]#[N:28])=[CH:19][CH:18]=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC>ClCCl.C1(C)C=CC=CC=1>[C:12]([C:3]1[CH:4]=[CH:5][C:6]([O:11][CH2:16][C:17]2[CH:18]=[CH:19][C:20]([CH:23]([O:32][CH:33]3[CH2:38][CH2:37][CH2:36][CH2:35][O:34]3)[C:24]3[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=3)[C:27]#[N:28])=[CH:21][CH:22]=2)=[C:7]([CH2:8][CH2:9][CH3:10])[C:2]=1[OH:1])(=[O:14])[CH3:13]

Participants

7

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 27751982',4'-Dihydroxy-3'-propylacetophenoneHCID 574382993-[(4-Hydroxymethyl-phenyl)-(tetrahydro-pyran-2-yloxy)-methyl]-benzonitrile

Product 1

HCID 666996043-[[4-(4-Acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenyl]-(tetrahydro-pyran-2-yloxy)-methyl]-benzonitrileYield 67%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

Stir a solution of 1-(2,4-dihydroxy-3-propyl-phenyl)-ethanone (1.75 g, 9 mmol), 3-[(4-hydroxymethyl-phenyl)-(tetrahydro-pyran-2-yloxy)-methyl]-benzonitrile (2.9 g, 9 mmol), toluene (10 mL), and dichloromethane (10 mL) at −20° C. Add 1,1′-(azodicarbonyl)dipiperidine (4.5 g, 18 mmol) followed by tributylphosphine (4.5 mL, 18 mmol) and allow the resulting yellow solution to stir at room temperature overnight. Concentrate the resulting thick reaction mixture and dilute with ether (50 mL). Cool the slurry to 0° C. with stirring, for 30 minutes. Filter the reaction mixture, concentrate, and purify via silica chromatography eluting with 1:1 hexanes:(5:4:1 hexanes:dichloromethane:ethyl acetate) to give the title compound (3 g, 67%), as an orange thick oil. LCMS (m/z) 498 M−1.

Workup

  1. concentrationConcentrate the resulting thick reaction mixture
  2. additiondilute with ether (50 mL)
  3. temperatureCool the slurry to 0° C.
  4. stirringwith stirring, for 30 minutes
  5. filtrationFilter the reaction mixture
  6. concentrationconcentrate
  7. custompurify via silica chromatography
  8. washeluting with 1:1 hexanes

Sources & evidence

ORD record
ord-401def85509a4aee949b4613a74cb666
Source dataset
uspto-grants-2010_10
Patent number
US07816523B2

Linked notes

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