Triethylamine → 1,1-Dimethylethyl (2S)-2-furo[2,3-c]pyridin-2-yl-1-pyrrolidinecarboxylate

HRID 611565Notes

Reaction equation

HRID 611565 reaction equation
[OH:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1I.C(N(CC)CC)C.[C:16]([N:23]1[CH2:27][CH2:26][CH2:25][C@H:24]1[C:28]#[CH:29])([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17]>CN(C=O)C.CCOCC.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.[Cu]I>[C:16]([N:23]1[CH2:27][CH2:26][CH2:25][C@H:24]1[C:28]1[O:1][C:2]2=[CH:3][N:4]=[CH:5][CH:6]=[C:7]2[CH:29]=1)([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 11030701(S)-N-Boc-2-ethynylpyrrolidineHCID 225035814-Iodopyridin-3-ol

Product 1

HCID 183962351,1-Dimethylethyl (2S)-2-furo[2,3-c]pyridin-2-yl-1-pyrrolidinecarboxylate

Reagents, catalysts & solvents 4

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

Procedure

A 829 mg (3.7 mmol) sample of 3-hydroxy-4-iodopyridine, from step 9b above, 130 mg (0.18 mmol) of (Ph3P)2PdCl2, 170 mg (0.74 mmol) of CuI, and 0.6 mL of triethylamine were combined in 10 mL of DMF at ambient temperature and stirred for 3 hours. To this mixture was added a solution of 1-BOC-2-(S)-ethynylpyrrolidine (1.5 g, 7.7 mmol, from Example 1c above) in 5 mL of DMF, and the reaction mixture was stirred at 60° C. for 16 hours. The reaction mixture was cooled to room temperature and diluted with ether. The ether layer was filtered, washed with 10% NaOH then 50% brine, dried over MgSO4, and concentrated. The residue was purified by chromatography on silica gel, eluting with 100:0 to 50:50 hexane:EtOAc to give the title compound.

Workup

  1. stirringthe reaction mixture was stirred at 60° C. for 16 hours
  2. filtrationThe ether layer was filtered
  3. washwashed with 10% NaOH
  4. dry with material50% brine, dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography on silica gel
  7. washeluting with 100:0 to 50:50 hexane

Sources & evidence

ORD record
ord-be2a1a9a5a634900aec9171d5fda877c
Source dataset
uspto-grants-1999_12
Patent number
US06001849

Reaction notes

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