Iodine → 5,6-dichloro-2-(1-t-butyloxycarbonyl-2-(S)-pyrrolidinyl)furo[3,2-b]pyridine

HRID 611578Notes

Reaction equation

HRID 611578 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:10])[C:5](I)=[N:6][C:7]=1[Cl:8].ClC1C=C(O)C=NC=1Cl.II.C(N(CC)CC)C.[C:29]([O:33][C:34]([N:36]1[CH2:40][CH2:39][CH2:38][C@H:37]1[C:41]#[CH:42])=[O:35])([CH3:32])([CH3:31])[CH3:30]>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.CCOCC>[Cl:8][C:7]1[N:6]=[C:5]2[CH:42]=[C:41]([C@@H:37]3[CH2:38][CH2:39][CH2:40][N:36]3[C:34]([O:33][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:35])[O:10][C:4]2=[CH:3][C:2]=1[Cl:1]

Participants

10

Reactant 5

HCID 807IodineHCID 8471TriethylamineHCID 11030701(S)-N-Boc-2-ethynylpyrrolidineHCID 143916722,3-Dichloro-5-hydroxypyridineHCID 195976065,6-Dichloro-2-iodopyridin-3-ol

Product 1

HCID 543798325,6-dichloro-2-(1-t-butyloxycarbonyl-2-(S)-pyrrolidinyl)furo[3,2-b]pyridineYield 44%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

5,6-Dichloro-2-iodo-3-pyridinol (750 mg, 2.6 mmol)(prepared by treatment of 5,6-dichloro-3-hydroxypyridine (Koch & Schnatterer, Synthesis 1990, 499) with I2 (ibid, p. 497), copper(I) iodide (89 mg, 0.47 mmol), bis(triphenylphosphine)palladium(II) chloride (91 mg, 0.13 mmol) and triethylamine (433 mL, 3.1 mmol) were combined in DMF (3.0 mL) and allowed to stir for 1 hour. 1-t-Butyloxycarbonyl-2-(S)-ethynylpyrrolidine (610 mg, 3.1 mmol) in DMF (1 mL) was added and the reaction mixture was heated to 60° C. for 16 hours. After cooling to ambient temperature, the reaction mixture was poured over Et2O/saturated K2CO3 solution and the phases separated. The organic phase was washed with brine:water (1:1) (4×), dried (MgSO4), concentrated and chromatographed (silica gel; EtOAc/hexane, 1:6) to afford an amber oil (408 mg, 44%): 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), 5.02 (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 separated
  3. washThe organic phase was washed with brine:water (1:1) (4×)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customchromatographed (silica gel; EtOAc/hexane, 1:6)

Sources & evidence

ORD record
ord-63803f8ac3d34096b26ac90fdac2254b
Source dataset
uspto-grants-1999_12
Patent number
US06001849

Reaction notes

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