Formic Acid → HCID 58001772, compound

HRID 420715Notes

Reaction equation

HRID 420715 reaction equation
Cl[C:2]1[C:7]([CH2:8][OH:9])=[CH:6][C:5]([F:10])=[C:4]([Cl:11])[N:3]=1.CCN(CC)CC.C(O)=O>O1CCOCC1.O.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>[Cl:11][C:4]1[N:3]=[CH:2][C:7]([CH2:8][OH:9])=[CH:6][C:5]=1[F:10]

Participants

7

Reactant 3

HCID 284Formic AcidHCID 8471TriethylamineHCID 23114857(2,6-Dichloro-5-fluoropyridin-3-yl)methanol

Product 1

HCID 58001772HCID 58001772, compoundYield 55.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of (2,6-dichloro-5-fluoro-3-pyridinyl)methanol (4.4 g, 22.45 mmol) in 1,4-dioxane (20 ml) was added Et3N (3.42 ml, 24.69 mmol), formic acid (0.947 ml, 24.69 mmol) and Pd(PPh3)4 (1.297 g, 1.122 mmol). The mixture was then heated at 110° C. for 6 h in a pressure tube. The crude was diluted with H2O and extracted twice with EtOAc. The combined organic phases were washed with H2O and sat. NaCl, dried over Na2SO4 and concentrated under reduced pressure. The crude was purified by flash chromatography using Flashmaster II, a 70 g spherical silica gel cartridge and DCM/MeOH 98:2 as eluent to give 2.0 g (41%) of the title compound pure enough to be used in the next step.

Workup

  1. extractionextracted twice with EtOAc
  2. washThe combined organic phases were washed with H2O and sat. NaCl
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude was purified by flash chromatography

Sources & evidence

ORD record
ord-857a90cddc1c4aa7ac1e3413bf9bfc48
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

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