Acetic Acid → HCID 18700142, compound

HRID 2289311Notes

Reaction equation

HRID 2289311 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18](CC#N)=[C:17]([C:24]([F:27])([F:26])[F:25])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.CCN(C(C)C)C(C)C.C(OC(OC(OC(C)(C)C)=O)=O)(C)(C)C.[C:53]([OH:56])(=[O:55])[CH3:54]>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:54][C:53]([OH:56])=[O:55])=[C:17]([C:24]([F:27])([F:25])[F:26])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonateHCID 18700071HCID 18700071, compound

Product 1

HCID 18700142HCID 18700142, compound

Procedure

To a stirred solution of 4-(N-tert-butyloxy-carbonyl-4-piperidinyloxy)-2-trifluoromethylphenylacetonitrile (0.26 g, 0.87 mmol) from Step 5 above in acetic acid (10 mL) was added concentrated aqueous HCl (5 mL). The mixture was refluxed for 4 h. The solvents were removed under reduced pressure and the residue was stripped from DMF (2×). The residue was then dissolved in DMF (5 mL). DIEA (0.45 mL, 2.6 mmol) and di-tert-butyldicarbonate (0.21 g, 9.6 mmol) were added. The mixture was stirred at ambient temperature for 3 h. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc (50 mL) and 0.25 M aqueous citric acid (25 mL). The organic phase was washed with water (2×25 mL), dried (MgSO4), filtered, and the solvent was removed under reduced pressure to give 4-(N-tert-butyloxycarbonyl-4-piperidinyloxy)-2-trifluoromethylphenylacetic acid as an amorphous solid (HPLC retention time=10.1 min (method A)).

Workup

  1. temperatureThe mixture was refluxed for 4 h
  2. customThe solvents were removed under reduced pressure
  3. dissolutionThe residue was then dissolved in DMF (5 mL)
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was partitioned between EtOAc (50 mL) and 0.25 M aqueous citric acid (25 mL)
  6. washThe organic phase was washed with water (2×25 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-b327a37e08ab419eb85caaaa553fe4f0
Source dataset
uspto-grants-2000_07
Patent number
US06090805

Reaction notes

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