1,2-Dimethoxyethane → (1R,6S)-tert-butyl 8-(4-(dimethylamino)pyridin-2-yl)-3,8-diazabicyclo[4.2.0]octane-3-carboxylate

HRID 1193096Notes

Reaction equation

HRID 1193096 reaction equation
C[C:2]1[N:7]=[C:6]([N:8]2[C@@H:15]3[C@@H:10]([CH2:11][CH2:12][NH:13][CH2:14]3)[CH2:9]2)[CH:5]=[CH:4][CH:3]=1.ClC1C=C([N:23]([CH3:25])[CH3:24])C=CN=1.[CH3:26][C:27]([CH3:30])([O-:29])[CH3:28].[K+].[CH3:32][O:33]CCOC>O>[CH3:25][N:23]([CH3:24])[C:4]1[CH:3]=[CH:2][N:7]=[C:6]([N:8]2[C@@H:15]3[C@@H:10]([CH2:11][CH2:12][N:13]([C:32]([O:29][C:27]([CH3:30])([CH3:28])[CH3:26])=[O:33])[CH2:14]3)[CH2:9]2)[CH:5]=1

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 109864952-Chloro-4-(dimethylamino)pyridineHCID 23665647Potassium tert-butoxideHCID 67116915(1R,6S)-8-(6-Methylpyridin-2-yl)-3,8-diazabicyclo[4.2.0]octane

Product 1

HCID 67117087(1R,6S)-tert-butyl 8-(4-(dimethylamino)pyridin-2-yl)-3,8-diazabicyclo[4.2.0]octane-3-carboxylateYield 52%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a microwave safe vial was added Intermediate 40 (200 mg, 0.94 mmol), 2-chloro-N,N-dimethylpyridin-4-amine (134 mg, 0.85 mmol), chloro[(1,2,3-n)-3-phenyl-2-propenyl][1,3-bis(2,6-di-1-propylphenyl)-4,5-dihydroimidazol-2-ylidene]palladium(II) (5.6 mg, 0.0086 mmol), potassium tert-butoxide (96.1 mg, 0.85 mmol) and DME (8 mL). The resulting mixture was heated to 100° C. After 1 hour the mixture was allowed to cool to ambient temperature at which time water (20 mL) was added. The aqueous layer was extracted with DCM (15 mL) three times. The organic layers were combined, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude residue was purified by reverse-phase HPLC (basic) to yield (1R,6S)-tert-butyl 8-(4-(dimethylamino)pyridin-2-yl)-3,8-diazabicyclo[4.2.0]octane-3-carboxylate (150 mg, 52%). MS (ESI) mass calcd. for C18H28N4O2, 332.2; m/z found, 333.2 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.84 (d, J=5.7 Hz, 1H), 6.02 (d, J=5.6 Hz, 1H), 5.45-5.31 (m, 1H), 4.47-4.35 (m, 1H), 4.09-3.96 (m, 1H), 3.91 (t, J=7.7 Hz, 1H), 3.86-3.72 (m, 2H), 3.55-3.26 (m, 2H), 2.95 (s, 6H), 2.85-2.70 (m, 1H), 2.06-1.95 (m, 1H), 1.90-1.84 (m, 1H), 1.45-1.29 (m, J=52.5 Hz, 9H).

Workup

  1. additionwas added
  2. extractionThe aqueous layer was extracted with DCM (15 mL) three times
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude residue was purified by reverse-phase HPLC (basic)

Sources & evidence

ORD record
ord-4f0d8f5c41c64ef89390c426fea6d741
Source dataset
uspto-grants-2014_03
Patent number
US08680275B2

Reaction notes

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