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

HRID 1527048Notes

Reaction equation

HRID 1527048 reaction equation
I[C:2]1[C:3]([NH:8][C@@H:9]([CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH3:10])=[N:4][CH:5]=[CH:6][CH:7]=1.C1(C2C=CC=CC=2)C(O)=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].O[C:37]([CH3:44])=[CH:38][C:39]([O:41][CH2:42][CH3:43])=[O:40]>C1COCC1.[Cu]I>[CH3:44][C:37]1[N:8]([C@@H:9]([CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH3:10])[C:3]2=[N:4][CH:5]=[CH:6][CH:7]=[C:2]2[C:38]=1[C:39]([O:41][CH2:42][CH3:43])=[O:40]

Participants

7

Reactant 4

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

Product 1

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-9375be7dd8384e1286aa7f9ee3926c3e
Source dataset
uspto-grants-2015_07
Patent number
US09085583B2

Reaction notes

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