Potassium Carbonate → 3-(trifluoromethoxy)phenyl (7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]-hexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

HRID 1184588Notes

Reaction equation

HRID 1184588 reaction equation
[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:22][N:14]4[CH2:15][CH2:16][N:17]([C:19](Cl)=[O:20])[CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.[F:23][C:24]([F:34])([F:33])[O:25][C:26]1[CH:27]=[C:28]([OH:32])[CH:29]=[CH:30][CH:31]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:22][N:14]4[CH2:15][CH2:16][N:17]([C:19]([O:32][C:28]5[CH:29]=[CH:30][CH:31]=[C:26]([O:25][C:24]([F:23])([F:33])[F:34])[CH:27]=5)=[O:20])[CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27332613-(Trifluoromethoxy)phenolHCID 86680508(7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]hexahydropyrrolo[1,2-a]-pyrazine-2(1H)-carbonyl chloride

Product 1

HCID 866805093-(trifluoromethoxy)phenyl (7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]-hexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the product from Example 114A (26 mg, 0.081 mmol) and 3-(trifluoromethoxy)phenol (14 mg, 0.081 mmol) in anhydrous N,N-dimethylformamide (0.8 mL) was added potassium carbonate (17 mg, 0.12 mmol), and the resulting mixture was stirred at ambient temperature for 16 hours. The mixture was partitioned between ethyl acetate and water, and the organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-60% ethyl acetate in hexanes to give the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 0.89-1.01 (m, 4 H), 1.83-2.09 (m, 3 H), 2.30-2.59 (m, 3 H), 2.60-2.93 (m, 1 H), 2.97-3.38 (m, 2 H), 3.76 (dd, J=9.9, 6.7 Hz, 1 H), 4.15-4.29 (m, 1 H), 4.30-4.45 (m, 1 H), 5.38 (q, J=5.8 Hz, 1 H), 7.00-7.13 (m, 3 H), 7.37 (t, J=8.1 Hz, 1 H), 7.95 (d, J=1.2 Hz, 1 H), 8.04 (d, J=1.2 Hz, 1 H); MS (ESI) m/z 465.0 (M+H)+.

Workup

  1. customThe mixture was partitioned between ethyl acetate and water
  2. extractionthe organic extract
  3. dry with materialwas dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d2c1de8ac4394261aa2be8712566b57e
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

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