Hydrochloric Acid → (R)-1-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-2,3-

HRID 1500200Notes

Reaction equation

HRID 1500200 reaction equation
CC1(C)[O:6][C@@H:5]([C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]3[CH:20]=[CH:19][C:18]([O:21][C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)=[CH:17][CH:16]=3)[N:10]=2)=[O:8])[CH2:4][O:3]1.C(Cl)Cl.CO.Cl.O>O1CCOCC1.C(Cl)Cl.C([O-])(O)=O.[Na+]>[F:28][C:25]1[CH:24]=[CH:23][C:22]([O:21][C:18]2[CH:19]=[CH:20][C:15]([C:11]3[N:10]=[C:9]([C:7](=[O:8])[C@H:5]([OH:6])[CH2:4][OH:3])[CH:14]=[CH:13][CH:12]=3)=[CH:16][CH:17]=2)=[CH:27][CH:26]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 21226129Dichloromethane methanolHCID 89822495(R)-(2,2-dimethyl-1,3-dioxolan-4-yl)(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)methanone

Product 1

HCID 71722102(R)-1-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-2,3-Yield 28%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of (R)-(2,2-dimethyl-1,3-dioxolan-4-yl)(6-(4-(4-fluorophenoxyl)phenyl)pyridin-2-yl)methanone (0.621, g, 1.58, mmol) in an 85:15, mixture of DCM/MeOH (10, mL) was added 4M HCl in dioxane (2, mL, 8, mmol). After stirring overnight 0.5, mL, water was added to the reaction. After 3, more hours the reaction was diluted with 50, mL DCM and solid NaHCO3, was added. After the bubbling subsided, the reaction mixture was dried over Na2SO4, filtered, and evaporated in vacuo to a residue. The residue was chromatographed over silica gel with 10-75% acetone in hexanes. The product fractions were isolated and evaporated in vacuo. The residue was dissolved in acetone, evaporated in vacuo, dissolved in EtOAc and hexanes, evaporated in vacuo, treated with hexanes, and evaporated in vacuo. The material was dried under vacuum at 50° C. to give the product (R)-1-(6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)-2,3-dihydroxypropan-1-one as a glassy orange solid (0.155, g, 0.44, mmol, 28% yield). LC/MS: m/z=354.1, [M+H]+, ; 1H NMR (400, MHz, DMSO-d6): 8.23-8.17, (3 H, m), 8.08, (1 H, t, J=7.9, Hz), 7.88, (1 H, dd, J=7.7, Hz, 0.9, Hz), 7.32-7.25, (2 H, m), 7.20-7.15, (2 H, m), 7.12, (2 H, d, J=9.0, Hz), 5.54-5.49, (1 H, m), 5.09, (1 H, d, J=7.0, Hz), 4.78, (1 H, t, J=5.5, Hz), 3.93-3.81, (2 H, m). Unless otherwise indicated all 1H NMR chemical shifts reported herein are denoted by the delta (δ) scale.

Workup

  1. additionwas added
  2. dry with materialthe reaction mixture was dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated in vacuo to a residue
  5. customThe residue was chromatographed over silica gel with 10-75% acetone in hexanes
  6. customThe product fractions were isolated
  7. customevaporated in vacuo
  8. dissolutionThe residue was dissolved in acetone
  9. customevaporated in vacuo
  10. dissolutiondissolved in EtOAc
  11. customhexanes, evaporated in vacuo
  12. additiontreated with hexanes
  13. customevaporated in vacuo
  14. customThe material was dried under vacuum at 50° C.

Sources & evidence

ORD record
ord-a49d85b2d3f143c884ef14301c155784
Source dataset
uspto-grants-2015_12
Patent number
US09206127B2

Reaction notes

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