L-Hydroxyproline → HCID 86762602, compound

HRID 2405682Notes

Reaction equation

HRID 2405682 reaction equation
Cl.Br[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.[NH:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[NH2:10].C1[C@@H](C(O)=O)NC[C@@H]1O.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.CCOC(C)=O.[NH4+].[Cl-].[Cu]I>[N:6]1[CH:7]=[CH:8][C:3]([N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[NH2:10])=[CH:4][CH:5]=1

Participants

9

Reactant 4

HCID 5810L-HydroxyprolineHCID 10796Cesium carbonateHCID 70091tert-Butyl carbazateHCID 881004-Bromopyridinium chloride

Product 1

HCID 86762602HCID 86762602, compoundYield 40%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-bromo-pyridine hydrochloride salt (8.0 g), tert-butyl hydrazinecarboxylate (10.87 g), CuI (784 mg), L-4-hydroxyproline (1.08 g) and Cs2CO3 (33.50 g) in dry DMSO (41 mL) under N2 was heated at 80° C. with efficient stirring for 5-6 hrs. After cooled to rt, the reaction mixture was diluted with EtOAc (150 mL) and saturated NH4Cl (150 mL). The organic layer was separated and the aqueous was extracted with EtOAc (3×150 mL). The combined organic layers were washed with brine (50 mL), dried (Na2SO4) and concentrated. The residue was purified by silica gel column chromatography (DCM to 10% MeOH/DCM gradient) to provide the title compound (3.4 g, 40%). ESI-MS (EI+, m/z): 210.0 [M+H]+. 1H NMR (300 MHz, DMSO) δ 8.38 (d, J=4.9 Hz, 2H), 7.64 (d, J=6.4 Hz, 2H), 5.12 (s, 2H), 3.34 (s, 1H), 1.51 (s, 9H).

Workup

  1. temperatureAfter cooled to rt
  2. customThe organic layer was separated
  3. extractionthe aqueous was extracted with EtOAc (3×150 mL)
  4. washThe combined organic layers were washed with brine (50 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography (DCM to 10% MeOH/DCM gradient)

Sources & evidence

ORD record
ord-34c159e8e38d493ab080ae19b692520b
Source dataset
uspto-grants-2014_08
Patent number
US08809314B1

Reaction notes

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