2-Bromopyrimidine → 4-Pyrimidin-2-ylethynyl-piperidine-1-carboxylic acid tert-butyl ester

HRID 1038043Notes

Reaction equation

HRID 1038043 reaction equation
Br[C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([C:21]#[CH:22])[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([C:21]#[C:22][C:2]2[N:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9]

Participants

5

Reactant 2

HCID 783452-Bromopyrimidine2×HCID 15550481tert-Butyl 4-ethynylpiperidine-1-carboxylate

Product 1

HCID 669398774-Pyrimidin-2-ylethynyl-piperidine-1-carboxylic acid tert-butyl esterYield 8%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst

Procedure

To a suspension of 2-bromopyrimidine (175 mg, 1.1 mmols), dichlorobis(triphenylphosphine)palladium(II) (35 mg, 0.05 mmols) and CuI (10 mg, 0.05 mmols) was added a solution of 4-ethynyl-piperidine-1-carboxylic acid tert-butyl ester (209 mg, 1 mmol). The mixture was stirred overnight, filtered through Celite, concentrated. The residue was partitioned between ethyl acetate and water, organic layer was isolated, dried (MgSO4), and concentrated. The residue was chromatographed on silica gel eluting with ethyl acetate in hexanes (1:1) to give un-reacted 2-bromopyrimidine (130 mg), then the title compound (23 mg). LCMS m/e (288, M+H).

Workup

  1. filtrationfiltered through Celite
  2. concentrationconcentrated
  3. customThe residue was partitioned between ethyl acetate and water
  4. customorganic layer was isolated
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe residue was chromatographed on silica gel eluting with ethyl acetate in hexanes (1:1)
  8. customto give

Sources & evidence

ORD record
ord-e45d7b86119f4a91afdadc37a01a965d
Source dataset
uspto-grants-2013_10
Patent number
US08546404B2

Reaction notes

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