Hydrochloric Acid → HCID 66731958, compound

HRID 1963340Notes

Reaction equation

HRID 1963340 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[Br-].[C:13]([C:17]1[CH:18]=[C:19]([CH:22]=[C:23]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH:24]=1)[CH2:20][Zn+])([CH3:16])([CH3:15])[CH3:14].Cl>O1CCCC1.CC(OC)(C)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:13]([C:17]1[CH:18]=[C:19]([CH:22]=[C:23]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH:24]=1)[CH2:20][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6])([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 178440982HCID 178440982, compound

Product 1

HCID 66731958HCID 66731958, compoundYield 90.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of methyl 2-chloroisonicotinate (4 g, 23.31 mmol) and Pd(PPh3)4 (0.539 g, 0.47 mmol) in tetrahydrofuran (120 mL) under nitrogen in a dried flask was added a freshly prepared solution of (3,5-di-tert-butylbenzyl)zinc(II) bromide (11.08 g, 31.78 mmol) in tetrahydrofuran (46 mL). The resulting bright yellow solution was heated to 60° C. for 35 min, then stirred at room temperature for 1 h. The reaction was quenched by addition of methanol (50 mL). The solution was diluted with EtOAc and washed with NH4Cl. The organic layer was dried over MgSO4, filtered and evaporated to yield a brown oil. The crude was redissolved in MTBE (180 mL) and solids were filtered off. Hydrogen chloride (4 M in dioxane, 6.42 mL, 25.66 mmol) was added dropwise during stirring and a suspension was formed. The suspension was stirred at room temperature for 10 min. The solid was collected by filtration and washed with MTBE. Redissolved in MTBE/satd NaHCO3. The phases were separated, the organic phase dried over Na2SO4, filtered and evaporated to yield methyl 2-(3,5-di-tert-butylbenzyl)isonicotinate (7.132 g, 90%) as a brown oil. 1H NMR (600 MHz, cdcl3) δ 1.28 (s, 18H), 3.89 (s, 3H), 4.19 (s, 2H), 7.11 (d, 2H), 7.27 (t, 1H), 7.64 (dd, 1H), 7.71 (s, 1H), 8.68 (d, 1H). MS m/z 340 (M+H)+

Workup

  1. customThe reaction was quenched by addition of methanol (50 mL)
  2. additionThe solution was diluted with EtOAc
  3. washwashed with NH4Cl
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto yield a brown oil
  8. filtrationsolids were filtered off
  9. stirringduring stirring
  10. customa suspension was formed
  11. stirringThe suspension was stirred at room temperature for 10 min
  12. filtrationThe solid was collected by filtration
  13. washwashed with MTBE
  14. dissolutionRedissolved in MTBE/satd NaHCO3
  15. customThe phases were separated
  16. dry with materialthe organic phase dried over Na2SO4
  17. filtrationfiltered
  18. customevaporated

Sources & evidence

ORD record
ord-1cf9b69453b942deb1a93c51fabee79f
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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