Potassium Carbonate → HCID 59330542, compound

HRID 1660726Notes

Reaction equation

HRID 1660726 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:13][CH2:12][N:11]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:5]=[N:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH2:46]([OH:52])[CH2:47][CH2:48][CH2:49][C:50]#[CH:51]>COCCOC.O.[Pd].[Cu]I>[OH:52][CH2:46][CH2:47][CH2:48][CH2:49][C:50]#[C:51][C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:13][CH2:12][N:11]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:5]=[N:6][CH:7]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 702345-Hexyn-1-olHCID 10688713(S)-Tert-butyl 2-(((5-bromopyridin-3-YL)oxy)methyl)azetidine-1-carboxylate

Product 1

HCID 59330542HCID 59330542, compoundYield 83%

Reagents, catalysts & solvents 4

HCID 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) -azetidinylmethoxy)pyridine (720 mg, 2.1 mmol), K2CO3 (725 mg, 5.25 mmol), PPh3 (50 mg) in DME (5 mL) and H2O (5 mL) was added 10% Pd/C (50 mg) and CuI (50 mg). The mixture was stirred at room temperature for 30 min under argon, then 5-hexyn-1-ol (0.8 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 (1:2) and then EtOAc to give an oil (630 mg, 83%), [α]D−37.1 (c 1.9, CHCl3). 1H NMR (CDCl3) δ 8.22 (d, 2H, J=2.1 Hz), 7.24 (t, 1H, J=2.1 Hz), 4.50 (m, 1H), 4.32 (m, 1M), 4.11 (dd, 1H, J=10.2, 3.0 Hz), 3.88 (t, 2H, J=7.5 Hz), 3.75-3.65 (m, 2H), 2.47 (t, 2H, J=6.9 Hz), 2.41-2.20 (m, 2H), 1.95 (s, 1H), 1.80-1.64 (m, 4H), 1.42 (s, 9H); 13C NMR (CDCl3) δ 156.13, 154.40, 144.75, 137.13, 123.26, 121.18, 93.48, 79.76, 77.45, 68.68, 62.20, 60.00, 47.06, 31.82, 28.36, 24.80, 19.18, 19.01.

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 (1:2)

Sources & evidence

ORD record
ord-22160f29d9ed49d4938b17db6eaae934
Source dataset
uspto-grants-2011_10
Patent number
US08030300B2

Reaction notes

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