Trifluoroacetic acid → HCID 60196780, compound

HRID 1523409Notes

Reaction equation

HRID 1523409 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[NH:22][C:23](=[O:31])[CH2:24][N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12](OC(C)(C)C)=O)[CH2:8][CH2:7]1.FC(F)(F)C(O)=O.[C:39]1(=O)[CH2:42]C[CH2:40]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(Cl)CCl>[CH:12]1([N:9]2[CH2:10][CH2:11][CH:6]([O:5][C:4]3[CH:19]=[CH:20][C:21]([NH:22][C:23](=[O:31])[CH2:24][N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[C:2]([F:1])[CH:3]=3)[CH2:7][CH2:8]2)[CH2:42][CH2:39][CH2:40]1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 14496CyclobutanoneHCID 5049666Sodium triacetoxyborohydrideHCID 86718434HCID 86718434, compound

Product 1

HCID 60196780HCID 60196780, compoundYield 55.5%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-Butyl 4-[3-fluoro-4-(2-(morpholin-4-yl)acetylamino) phenoxy]piperidine-1-carboxylate (3.1 g, 0.007 moles, obtained in above step) in dichloromethane (25 mL) was added trifluoroacetic acid (8.1 g, 0.071 moles) and stirred reaction mass overnight at room temperature. After completion of reaction, solvent was evaporated under vacuum and the residue, thus obtained, was basified with 10% caustic lye solution. Extracted the reaction mass with ethyl acetate twice, the combined organic layer dried over sodium sulphate and evaporated under reduced pressure. The crude product, thus obtained, was treated with cyclobutanone (0.6 g, 0.008 moles), in ethylene dichloride (30 mL), and stirred for 4 hours at room temperature. Sodium triacetoxyborohydride (3 g, 0.014 moles) was added to reaction mass in a single lot and the mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched in water and basified with lye solution. The layers were separated and the aqueous layer was extracted with dichloromethane twice. The combined organic layers were dried over sodium sulfate, concentrated under vacuum and the residual mass was further purified by flash chromatography (dichloromethane: triethylamine, 9.5:0.5) to obtain the title compound 1.52 g (Yield: 55%).

Workup

  1. customreaction mass overnight at room temperature
  2. customAfter completion of reaction, solvent
  3. customwas evaporated under vacuum
  4. customthe residue, thus obtained
  5. extractionExtracted the reaction mass with ethyl acetate twice
  6. dry with materialthe combined organic layer dried over sodium sulphate
  7. customevaporated under reduced pressure
  8. customThe crude product, thus obtained
  9. stirringstirred for 4 hours at room temperature
  10. stirringthe mixture was stirred at room temperature for 2 hours
  11. customThe reaction mixture was quenched in water
  12. customThe layers were separated
  13. extractionthe aqueous layer was extracted with dichloromethane twice
  14. dry with materialThe combined organic layers were dried over sodium sulfate
  15. concentrationconcentrated under vacuum
  16. customthe residual mass was further purified by flash chromatography (dichloromethane: triethylamine, 9.5:0.5)

Sources & evidence

ORD record
ord-d004276c9ca3406a83192b197f4647ce
Source dataset
uspto-grants-2015_07
Patent number
US09079888B2

Reaction notes

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