Sodium Carbonate → tert-Butyl [3-(pyridin-3-yl)prop-2-yn-1-yl]carbamate

HRID 1913366Notes

Reaction equation

HRID 1913366 reaction equation
[CH2:1]([NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8])[C:2]#[CH:3].C(=O)([O-])[O-].[Na+].[Na+].Br[C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1>C(O)C.C(COC)OC.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.[Cu]I>[N:21]1[CH:22]=[CH:23][CH:24]=[C:19]([C:3]#[C:2][CH2:1][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:8])([CH3:10])[CH3:9])[CH:20]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 122863-BromopyridineHCID 11073648tert-butyl N-(prop-2-yn-1-yl)carbamate

Product 1

HCID 70832777tert-Butyl [3-(pyridin-3-yl)prop-2-yn-1-yl]carbamateYield 97.7%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 20074477Dimethoxyethane ethanolSolvent

Conditions

Temperature
90 °C

Procedure

To a pressure tube containing a magnetic stir bar was added 46 (202 mg, 1.3 mmol) and the vial was purged with argon. To the tube is added a solution of tetrakis(triphenylphosphine)palladium(0) (45 mg, 0.04 mmol) in ethanol/dimethoxyethane (1:1, 2 mL), sodium carbonate(aq) (2 M, 4 mL, 4 mmol), copper(I)iodide (46 mg, 0.24 mmol) and the vial was once again purged with argon. The resultant solution was stirred at room temperature for 5 min when 3-bromopyridine (483 μL, 5 mmol) was added as a neat oil. The tube was purged with argon, capped, heated to 90° C. and stirred for 1 h. The solution was cooled to room temperature and poured into a flask containing anhydrous sodium sulfate (5 g). The solution was dried for 10 min, filtered and the solvent was removed in vacuo. The crude material was chromatographed on silica gel (CH3OH/CHCl3, 5/95, Rf=0.43) to afford the title compound 47 (295 mg, 97% yield) as a brown solid: mp=74-78° C.; 1H NMR (CDCl3) δ 8.63 (m, 1H), 8.51 (m, 1H), 7.67 (m, 1H), 7.22 (m, 1H), 5.05 (br s, 1H), 4.15 (m, 2H), 1.45 (s, 9H); LRMS (ESI) m/z calcd for C13H16N2O2 [M+H]+ 233. found 233; m/z calcd for C9H9N2O2 [M+H−CH2C(CH3)2]+ 177. found 177; m/z calcd for C8H9N2 [M+H−t-Boc]+ 133. found 133.

Workup

  1. additionTo a pressure tube containing a magnetic stir bar
  2. customthe vial was purged with argon
  3. customthe vial was once again purged with argon
  4. additionwas added as a neat oil
  5. customThe tube was purged with argon
  6. customcapped
  7. temperatureThe solution was cooled to room temperature
  8. additionpoured into a flask
  9. additioncontaining anhydrous sodium sulfate (5 g)
  10. customThe solution was dried for 10 min
  11. filtrationfiltered
  12. customthe solvent was removed in vacuo
  13. customThe crude material was chromatographed on silica gel (CH3OH/CHCl3, 5/95, Rf=0.43)

Sources & evidence

ORD record
ord-17df983c9d1b4643b8ff6daeb6bf115c
Source dataset
uspto-grants-2013_12
Patent number
US08609708B2

Reaction notes

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