Trifluoroacetic acid → HCID 16097319, compound

HRID 2266960Notes

Reaction equation

HRID 2266960 reaction equation
[F:1][CH:2]([F:29])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[N:14]=[CH:13][N:12]=[C:11]([N:15]2[CH2:20][CH2:19][CH:18]([NH:21][C:22](=[O:28])[O:23][C:24](C)(C)[CH3:25])[CH2:17][CH2:16]2)[CH:10]=1.FC(F)(F)[C:32](O)=[O:33].C([O-])(O)=O.[Na+].C(N(CC)CC)C.ClC(OCCOC)=O>O.C(Cl)Cl>[F:1][CH:2]([F:29])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[N:14]=[CH:13][N:12]=[C:11]([N:15]2[CH2:20][CH2:19][CH:18]([NH:21][C:22](=[O:28])[O:23][CH2:24][CH2:25][O:33][CH3:32])[CH2:17][CH2:16]2)[CH:10]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 694002-Methoxyethyl chloroformateHCID 516892Sodium BicarbonateHCID 58857067HCID 58857067, compound

Product 1

HCID 16097319HCID 16097319, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl 1-(6-(2-(difluoromethyl)phenyl)pyrimidin-4-yl)piperidin-4-ylcarbamate (0.05 g, 0.1 mmol), CH2Cl2 (0.5 mL), and trifluoroacetic acid (0.5 mL) was stirred at room temperature for 30 minutes. The reaction was made basic with saturated aqueous NaHCO3 and extracted with CH2Cl2. The combined extracts were dried over Na2SO4 and evaporated. The residue was dissolved in CH2Cl2 (0.4 mL) and triethylamine (16 μL, 0.12 mmol), and the reaction was cooled in a dry ice/acetone bath. 2-Methoxyethyl chloroformate (16 μL, 0.1 mmol) was added, and the reaction was stirred for 15 minutes. The reaction was diluted with H2O and extracted with CH2Cl2. The combined extracts were washed with water, dried over Na2SO4 and evaporated. The residue was purified by reverse phase HPLC (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)) to give 2-methoxyethyl 1-(6-(2-(difluoromethyl)phenyl)pyrimidin-4-yl)piperidin-4-ylcarbamate. LC/MS: m/z 407.4 (M+H)+ at 2.18 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. extractionextracted with CH2Cl2
  2. dry with materialThe combined extracts were dried over Na2SO4
  3. customevaporated
  4. dissolutionThe residue was dissolved in CH2Cl2 (0.4 mL)
  5. extractionextracted with CH2Cl2
  6. washThe combined extracts were washed with water
  7. dry with materialdried over Na2SO4
  8. customevaporated
  9. customThe residue was purified by reverse phase HPLC (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA))

Sources & evidence

ORD record
ord-95eedbe31b3a4260a2f3543bd30550b8
Source dataset
uspto-grants-2010_12
Patent number
US07858786B2

Reaction notes

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