Potassium Carbonate → HCID 67429189, compound

HRID 1660727Notes

Reaction equation

HRID 1660727 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:5]=[N:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].[CH2:28]([OH:34])[CH2:29][CH2:30][CH2:31][C:32]#[CH:33]>COCCOC.O.[Pd].[Cu]I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:34][CH2:28][CH2:29][CH2:30][CH2:31][C:32]#[C:33][C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:5]=[N:6][CH:7]=1

Participants

9

Reactant 3

HCID 11430Potassium CarbonateHCID 702345-Hexyn-1-olHCID 15480235(S)-2-((5-Bromopyridin-3-yloxy)methyl)pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 67429189HCID 67429189, compoundYield 95%

Reagents, catalysts & solvents 5

HCID 11776TriphenylphosphineCatalystHCID 23938PalladiumCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a stirred solution of 5-bromo-3-(1-tert-butoxycarbonyl-2(S)-pyrrolidinylmethoxy)pyridine (800 mg, 2.24 mmol), K2CO3 (745 mg, 5.40 mmol), PPh3 (55 mg) in DME (4 mL) and H2O (4 mL) was added 10% Pd/C (55 mg) and CuI (55 mg). The mixture was stirred at room temperature for 30 ml under argon, then 5-hexyn-1-ol (1.0 mL) was added. The reaction mixture was refluxed for 72 h. After cooled, the mixture was filtered through Celite and washed with EtOAc. The filtrate was concentrated in vacuo. The residue was purified by chromatography with hexane-EtOAc (1:1) to give an oil (800 mg, 95%), [α]D=−35.5 (c 2.2, CHCl3). 1H NMR (CDCl3) δ 8.19 (m, 2H), 7.23 (m, 1H), 4.14 (m, 2H), 4.05-3.75 (m, 1H), 3.75-3.69 (m, 2H), 3.50-3.25 (m, 2H), 2.47 (t, 2H, J=6.6 Hz), 2.10-1.64 (m, 9H), 1.47 (s, 9H); 13C NMR (CDCl3) δ154.70, 154.36, 144.76 and 144.49, 137.29 and 137.00, 123.04, 121.15, 93.32, 79.96 and 79.56, 68.69 and 68.33, 62.28, 55.94 and 55.64, 46.97 46.59, 31.82, 28.51, 28.00, 24.79, 23.84, 22.83, 19.20.

Workup

  1. temperatureThe reaction mixture was refluxed for 72 h
  2. temperatureAfter cooled
  3. filtrationthe mixture was filtered through Celite
  4. washwashed with EtOAc
  5. concentrationThe filtrate was concentrated in vacuo
  6. customThe residue was purified by chromatography with hexane-EtOAc (1:1)

Sources & evidence

ORD record
ord-69c6a8d58cb94c648843b3269c26335f
Source dataset
uspto-grants-2011_10
Patent number
US08030300B2

Reaction notes

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