(1,1'-Biphenyl)-2-ol → HCID 131733198, compound

HRID 2206561Notes

Reaction equation

HRID 2206561 reaction equation
[CH3:1][C:2]([S@@:5]([NH2:7])=[O:6])([CH3:4])[CH3:3].I[C:9]1[C:10]([NH:15][C@@H:16]([CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[CH3:17])=[N:11][CH:12]=[CH:13][CH:14]=1.C1(C2C=CC=CC=2)C(O)=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].O[C:44]([CH3:51])=[CH:45][C:46]([O:48][CH2:49][CH3:50])=[O:47]>C1COCC1.[Cu]I>[CH3:1][C:2]([S@@:5]([NH2:7])=[O:6])([CH3:4])[CH3:3].[CH3:51][C:44]1[N:15]([C@@H:16]([CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[CH3:17])[C:10]2=[N:11][CH:12]=[CH:13][CH:14]=[C:9]2[C:45]=1[C:46]([O:48][CH2:49][CH3:50])=[O:47]

Participants

9

Reactant 5

HCID 7017(1,1'-Biphenyl)-2-olHCID 10796Cesium carbonateHCID 11355477tert-Butylsulfinamide, (S)-(-)-HCID 54692957HCID 54692957, compoundHCID 89739691HCID 89739691, compound

Product 2

HCID 11355477tert-Butylsulfinamide, (S)-(-)-HCID 131733198HCID 131733198, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A re-sealable vial containing (S)- or (R)-3-iodo-N-(1-(tetrahydro-2H-pyran-4-yl)ethyl)pyridin-2-amine (0.333 g, 1.002 mmol), copper(I) iodide (0.0084 g, 0.044 mmol), biphenyl-2-ol (0.018 g, 0.106 mmol), and cesium carbonate (0.672 g, 2.062 mmol) was diluted with THF (3.5 mL). To the orange mixture was added ethyl 3-hydroxybut-2-enoate (0.25 mL, 1.977 mmol). The resultant blue-green contents were evacuated and purged with N2 (g) (3×). The vial was subsequently sealed and heated to 100° C. After 24 h, the reaction mixture was cooled to room temperature and filtered over a pad of Celite. The filter pad was washed with EtOAc (3×) and the filtrate was concentrated to give a thick brown oil. The resultant oil was purified on a Biotage system (50 g, gradient elution 2% EtOAc: 98% Hexanes to 15% EtOAc: 85% Hexanes, then 15% EtOAc: 85% Hexanes). The product (S)- or (R)-ethyl 2-methyl-1-(1-(tetrahydro-2H-pyran-4-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylate (0.257 g, 0.812 mmol, 81.0% yield) was isolated as a white foam. LRMS (M+H+) m/z: calcd 317.2. found 317.

Workup

  1. customThe resultant blue-green contents were evacuated
  2. custompurged with N2 (g) (3×)
  3. customThe vial was subsequently sealed
  4. temperaturethe reaction mixture was cooled to room temperature
  5. filtrationfiltered over a pad of Celite
  6. washThe filter pad was washed with EtOAc (3×)
  7. concentrationthe filtrate was concentrated
  8. customto give a thick brown oil
  9. customThe resultant oil was purified on a Biotage system (
  10. wash50 g, gradient elution 2% EtOAc

Sources & evidence

ORD record
ord-75b0620c18c34d0ebd986538353410c0
Source dataset
uspto-grants-2016_06
Patent number
US09371331B2

Reaction notes

Loading…