Water → 6-Cyclopropylmethoxy-5-(tetrahydro-pyran-4-yl)-pyridine-2-carboxylic acid

HRID 631967Notes

Reaction equation

HRID 631967 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:13]([OH:15])=[O:14])=[N:6][C:7]=1[O:8][CH2:9][CH:10]1[CH2:12][CH2:11]1.[O:16]1[CH2:21][CH:20]=[C:19](B2OC(C)(C)C(C)(C)O2)[CH2:18][CH2:17]1.C(=O)([O-])[O-].[Na+].[Na+].O>CN(C=O)C.C(Cl)Cl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH:10]1([CH2:9][O:8][C:7]2[N:6]=[C:5]([C:13]([OH:15])=[O:14])[CH:4]=[CH:3][C:2]=2[CH:19]2[CH2:20][CH2:21][O:16][CH2:17][CH2:18]2)[CH2:12][CH2:11]1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 710875435-Bromo-6-cyclopropylmethoxy-pyridine-2-carboxylic acid

Product 1

HCID 710874016-Cyclopropylmethoxy-5-(tetrahydro-pyran-4-yl)-pyridine-2-carboxylic acidYield 90.9%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

Under an atmosphere of nitrogen, a solution of 5-bromo-6-(cyclopropylmethoxy)-pyridine-2-carboxylic acid (300 mg, 1.1 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (278 mg, 1.3 mmol), 1,1′-bis(diphenylphosphino) ferrocene-palladium(II)dichloride methylene chloride complex (CAN 95464-05-4, 45 mg, 0.06 mmol) and sodium carbonate (964 mg, 9.1 mmol) in DMF (10 mL) was heated to 100° C. overnight. The reaction mixture was poured into water, extracted with ethyl acetate (30 mL), the pH of the aqueous layer was adjusted to 2 by addition of 1 N hydrochloric acid and the resulting mixture was extracted with ethyl acetate (3×30 mL). The combined organic extracts were washed six times with brine, dried over anhydrous sodium sulfate and evaporated. The residue was purified by column chromatography (silica gel, 8 g, 30% ethyl acetate in petroleum ether) to yield the title compound (0.15 g, 1 mmol, 49.4%) as white solid; MS (EI): m/e 276.0 [M+H]+.

Workup

  1. extractionextracted with ethyl acetate (30 mL)
  2. additionthe pH of the aqueous layer was adjusted to 2 by addition of 1 N hydrochloric acid
  3. extractionthe resulting mixture was extracted with ethyl acetate (3×30 mL)
  4. washThe combined organic extracts were washed six times with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated
  7. customThe residue was purified by column chromatography (silica gel, 8 g, 30% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-47e4695318804e32bc745e27b3675514
Source dataset
uspto-grants-2016_04
Patent number
US09321727B2

Reaction notes

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