Potassium Carbonate → {(1S,4S)-4-[2-(2-Methoxy-acetylamino)-pyridin-4-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-carbamic acid tert-butyl ester

HRID 630707Notes

Reaction equation

HRID 630707 reaction equation
[C:1]([O:5][C:6](=[O:26])[NH:7][C@@H:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C@@H:11]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21](Cl)[CH:20]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:27][O:28][CH2:29][C:30]([NH2:32])=[O:31].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6](=[O:26])[NH:7][C@@H:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C@@H:11]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21]([NH:32][C:30](=[O:31])[CH2:29][O:28][CH3:27])[CH:20]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 1400602-MethoxyacetamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86686964[(1S,4S)-4-(2-Chloro-pyridin-4-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-carbamic acid tert-butyl ester

Product 1

HCID 86686965{(1S,4S)-4-[2-(2-Methoxy-acetylamino)-pyridin-4-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-carbamic acid tert-butyl esterYield 44%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

Intermediate 10b (562 mg, 1.50 mmol), 2-methoxyacetamide (334 mg, 3.75 mmol), Xantphos (173 mg, 0.30 mmol) and potassium carbonate (518 mg, 3.75 mmol) were suspended in 1,4-dioxane (20 mL), warmed, degassed, and placed under argon. To this mixture palladium acetate (34.0 mg, 0.15 mmol) was added. The mixture was degassed and then heated at reflux for 17 h. After cooling, the mixture was filtered through Celite, washing with DCM, and evaporated to a yellow gum. Purification by FCC, eluting with 0-100% ethyl acetate in cyclohexane, gave the title compound as a white foam (281 mg, 44%). LCMS (Method 3): Rt 3.27 min, m/z 450.2 [MNa+].

Workup

  1. temperaturewarmed
  2. customdegassed
  3. customThe mixture was degassed
  4. temperatureheated
  5. temperatureat reflux for 17 h
  6. temperatureAfter cooling
  7. filtrationthe mixture was filtered through Celite
  8. washwashing with DCM
  9. customevaporated to a yellow gum
  10. customPurification by FCC
  11. washeluting with 0-100% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-88247a2469724d65a3c34caeaa51e1da
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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