Piperidine → HCID 178451935, compound

HRID 538732Notes

Reaction equation

HRID 538732 reaction equation
N1C=CN=C1[C@@H]1CCCN1C(OC(C)(C)C)=O.[I:18][C:19]1[N:20]=[C:21]([C@@H:25]2[CH2:29][CH2:28][CH2:27][N:26]2[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[NH:22][C:23]=1I.P(C(C)(C)C)(C(C)(C)C)C(C)(C)C.N1CCCCC1>CN(C=O)C.[Cu]I>[I:18][C:19]1[N:20]=[C:21]([C@@H:25]2[CH2:29][CH2:28][CH2:27][N:26]2[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[NH:22][CH:23]=1

Participants

7

Reactant 4

HCID 8082PiperidineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 49783269tert-Butyl (2S)-2-(1H-imidazol-2-yl)pyrrolidine-1-carboxylateHCID 59449990(S)-tert-butyl 2-(4,5-diiodo-1H-imidazol-2-yl)-pyrrolidine-1-carboxylate

Product 1

HCID 178451935HCID 178451935, compoundYield 99%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 5 (630 mg, 1.53 mmol), 6 (520 mg, 1.53 mmol), Pd (PPh3)2Cl2 (56 mg, 0.080 mmol) and CuI (8 mg, 0.04 mmol), P(t-Bu)3 (1.1 mL, 0.31 mmol), piperidine (1.05 mL, 4.60 mmol) in DMF (20 mL) was stirred at 40° C. for 12 h. The reaction mixture was partitioned between H2O and DCM. The organic layer was washed with H2O (4×50 mL) and brine (15 mL), dried over anhydrous Na2SO4, filtered and then concentrated in vacuo. The residue was purified by silica gel chromatography (DCM/MeOH=50/1 (v/v)) to afford 7 (550 mg, 50% yield) as a pale yellow solid. LC-MS (ESI) m/z 623.3 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between H2O and DCM
  2. washThe organic layer was washed with H2O (4×50 mL) and brine (15 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (DCM/MeOH=50/1 (v/v))

Sources & evidence

ORD record
ord-9daf7b283903470792e61a9c1d5fb06d
Source dataset
uspto-grants-2014_10
Patent number
US08865756B2

Reaction notes

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