(S)-N-Boc-2-ethynylpyrrolidine → HCID 18396228, compound

HRID 611569Notes

Reaction equation

HRID 611569 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](I)[C:5]([OH:9])=[CH:4][CH:3]=1.[C:10]([N:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[C:22]#[CH:23])([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11]>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:10]([N:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[C:22]1[O:9][C:5]2[C:6](=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH:23]=1)([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11]

Participants

7

Reactant 2

HCID 11030701(S)-N-Boc-2-ethynylpyrrolidineHCID 234331586-Chloro-2-iodo-3-hydroxypyridine

Product 1

HCID 18396228HCID 18396228, compound

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 3.07 g (12.0 mmol) sample of 6-chloro-2-iodo-3-pyridinol, from step 11c above, was dissolved in 10 mL of DMF, and (Ph3P)2PdCl2 (0.38 g, 0.50 mmol), CuI (0.380 g, 1.98 mmol) and triethylanue (1.7 mL, 12 mmol) were added. The mixture was stirred under N2 at room temperature for 1 hour, then 1.95 g (10.0 mmol) of 1-BOC-2-(S)-ethynylpyrrolidine, from Example 1a above, dissolved in 5 mL of DMF, was added carefully. The reaction mixture was stirred at 60° C. for 16 hours, cooled to room temperature, diluted with ether, washed with 50% brine and dried over MgSO4, then the solvent was removed. The residue was chromatographed on silica gel, eluting with 100:0 to 50:50 hexane:EtOAc to give 1.54 g of title compound: 1H NMR (DMSO, 300 MHz, 130° C.) δ 1.37 (two s, 9H), 1.89-2.07 (m, 3H), 2.37 (m, 1H), 3.40-3.54 (m, 1H), 4.98 (m, 1H), 6.72 (s, 1H), 7.26-7.29 (d, 1H, J=8.6 Hz), 7.93-7.96 (d, 1H, J=8.6 Hz); MS m/z: 323 (M+H)+.

Workup

  1. additionwas added carefully
  2. stirringThe reaction mixture was stirred at 60° C. for 16 hours
  3. temperaturecooled to room temperature
  4. washwashed with 50% brine
  5. dry with materialdried over MgSO4
  6. customthe solvent was removed
  7. customThe residue was chromatographed on silica gel
  8. washeluting with 100:0 to 50:50 hexane

Sources & evidence

ORD record
ord-1a2dcc8ed35b4402be3e7fb728d3b393
Source dataset
uspto-grants-1999_12
Patent number
US06001849

Reaction notes

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