Tert-Butylamine → t-Butyl 5-(6-hydroxymethylpyridin-2-yl)pent-4-ynoate

HRID 1172258

Reaction equation

HRID 1172258 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][OH:9])[N:3]=1.[C:10]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])(=[O:15])[CH2:11][CH2:12][C:13]#[CH:14].C(N)(C)(C)C>[Cu]I.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.CN(C=O)C>[OH:9][CH2:8][C:4]1[N:3]=[C:2]([C:14]#[C:13][CH2:12][CH2:11][C:10]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 3

HCID 6385Tert-ButylamineHCID 3517811(6-Bromopyridin-2-yl)methanolHCID 108773414-Pentynoic acid, 1,1-dimethylethyl ester

Product 1

HCID 58105203t-Butyl 5-(6-hydroxymethylpyridin-2-yl)pent-4-ynoateYield 56.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a 200 mL round-bottom flask, 3.49 g of 2-bromopyridine-6-methanol, 3.0 g of t-butyl 4-pentynoate, 190 mg of BHT, 1.17 g of copper(I) iodide, 877 mg of tetrakis(triphenylphosphine)palladium(0), 2.72 g of t-butylamine and 56 mL of DMF were added, and the mixture was stirred under argon atmosphere at 80° C. for 6 hours. After the DMF was removed under reduced pressure from the reaction mixture, saturated aqueous sodium bicarbonate was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and then the solvent was removed. The residue was purified by chromatography on silica gel (n-hexane-ethyl acetate=2:1) to give 2.76 g of t-butyl 5-(6-hydroxymethylpyridin-2-yl)pent-4-ynoate as a yellow oil.

Workup

  1. customAfter the DMF was removed under reduced pressure from the reaction mixture, saturated aqueous sodium bicarbonate
  2. additionwas added
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was removed
  7. customThe residue was purified by chromatography on silica gel (n-hexane-ethyl acetate=2:1)

Sources & evidence

ORD record
ord-7e5a40fea3f542e6ad4cf74ba32c9a86
Source dataset
uspto-grants-2010_11
Patent number
US07834002B2

Linked notes

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