Diethyl Ether → 5,6-Dichloro-2-(1-t-butyloxycarbonyl-2-(R)-pyrrolidinyl)furo[3,2-b]pyridin

HRID 611585Notes

Reaction equation

HRID 611585 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:10])[C:5](I)=[N:6][C:7]=1[Cl:8].C(N(CC)CC)C.[C:18]([O:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][C@@H:26]1[C:30]#[CH:31])=[O:24])([CH3:21])([CH3:20])[CH3:19].CCOCC>CN(C=O)C.[Cu]I.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>[Cl:8][C:7]1[N:6]=[C:5]2[CH:31]=[C:30]([C@H:26]3[CH2:27][CH2:28][CH2:29][N:25]3[C:23]([O:22][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:24])[O:10][C:4]2=[CH:3][C:2]=1[Cl:1]

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 10262067tert-butyl (2R)-2-ethynylpyrrolidine-1-carboxylateHCID 195976065,6-Dichloro-2-iodopyridin-3-ol

Product 1

HCID 543798315,6-Dichloro-2-(1-t-butyloxycarbonyl-2-(R)-pyrrolidinyl)furo[3,2-b]pyridinYield 46.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

5,6-Dichloro-2-iodo-3-pyridinol (632 mg, 2.2 mmol), copper(I) iodide (75 mg, 0.40 mmol), bis(triphenylphosphine)palladium(II) chloride (77 mg, 0.11 mmol) and triethylamine (370 mL, 2.6 mmol) were combined in DMF (2.7 mL) and allowed to stir for 1 hour. 1-t-Butyloxycarbonyl-2-(R)-ethynylpyrrolidine (510 mg, 2.6 mmol) in DMF (1 mL) was added and the mixture was heated to 60° C. for 16 hours. After cooling to ambient temperature, the mixture was poured over Et2O/saturated K2CO3 solution and the phases were separated. The organic phase was washed with brine:water (1:1) (4×), dried (MgSO4) and concentrated. The residue was chromatographed (silica gel; EtOAc/hexane, 1:6) to afford an amber oil (365 mg, 46%): 1H NMR (CDCl3, 300 MHz) δ 1.32 and 1.45 (two br s, 9H), 1.95-2.40 (m, 4H), 3.45-3.74 (m, 2H), 4.92-5.13 (m, 1H), 6.62 (s, 1H), 7.81 (s, 1H); MS (CI/NH3) m/z: 357 (M+H)+.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customthe phases were separated
  3. washThe organic phase was washed with brine:water (1:1) (4×)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was chromatographed (silica gel; EtOAc/hexane, 1:6)

Sources & evidence

ORD record
ord-651de7232e62402a8d680c07a248cfc4
Source dataset
uspto-grants-1999_12
Patent number
US06001849

Reaction notes

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