2,5-Dibromopyridine → Benzyl 3-(5-bromopyridin-2-yl)prop-2-ynylcarbamate

HRID 49569Notes

Reaction equation

HRID 49569 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[C:9]([NH:19][CH2:20][C:21]#[CH:22])([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10]>C(NC(C)C)(C)C.C(OCC)(=O)C.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>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C:22]#[C:21][CH2:20][NH:19][C:9](=[O:10])[O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:3][CH:4]=1

Participants

7

Reactant 2

HCID 693532,5-DibromopyridineHCID 11137906Benzyl prop-2-yn-1-ylcarbamate

Product 1

HCID 21299382Benzyl 3-(5-bromopyridin-2-yl)prop-2-ynylcarbamateYield 73.8%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 7912DiisopropylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2,5-dibromopyridine (1.19 g), N-Cbz-propargylamine (1.04 g), Pd(PPh3)2Cl2 (73 mg), and CuI (10 mg) in diisopropylamine (20 mL) was stirred at ambient temperature for 3 hours under nitrogen. The mixture was diluted with ethyl acetate (50 mL). The mixture was filtered and washed with ethyl acetate (20 mL). The filtrate and wash were combined, concentrated under reduced pressure and triturated in MTBE to give crystalline 7-1 (1.28 g). The mother liquor was further purified by silica gel column chromatography using a mixture of MTBE: hexanes (1:1) to give an additional 280 mg of 7-1.

Workup

  1. filtrationThe mixture was filtered
  2. washwashed with ethyl acetate (20 mL)
  3. washThe filtrate and wash
  4. concentrationconcentrated under reduced pressure
  5. customtriturated in MTBE

Sources & evidence

ORD record
ord-26c2d7fafdc044be956e21bc0a6f0e9f
Source dataset
uspto-grants-2004_03
Patent number
US06706885B2

Reaction notes

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