Hydrochloric Acid → 4-{4-[3-(2-Chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-phenyl}-5,6-dihydro-2H-pyridine-1,3-dicarboxylic Acid 1-tert-butyl Ester

HRID 2428200Notes

Reaction equation

HRID 2428200 reaction equation
[Li+].[OH-].C[O:4][C:5]([C:7]1[CH2:8][N:9]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:10][CH2:11][C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]2[O:25][N:24]=[C:23]([C:26]3[C:31]([F:32])=[CH:30][CH:29]=[C:28]([F:33])[C:27]=3[Cl:34])[CH:22]=2)=[CH:15][CH:14]=1)=[O:6].Cl>C1COCC1>[C:38]([O:37][C:35]([N:9]1[CH2:10][CH2:11][C:12]([C:13]2[CH:14]=[CH:15][C:16]([O:19][CH2:20][C:21]3[O:25][N:24]=[C:23]([C:26]4[C:31]([F:32])=[CH:30][CH:29]=[C:28]([F:33])[C:27]=4[Cl:34])[CH:22]=3)=[CH:17][CH:18]=2)=[C:7]([C:5]([OH:6])=[O:4])[CH2:8]1)=[O:36])([CH3:41])([CH3:39])[CH3:40]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 671487834-{4-[3-(2-Chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-phenyl}-5,6-dihydro-2H-pyridine-1,3-dicarboxylic Acid 1-tert-butyl Ester 3-methyl Ester

Product 1

HCID 671489104-{4-[3-(2-Chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-phenyl}-5,6-dihydro-2H-pyridine-1,3-dicarboxylic Acid 1-tert-butyl Ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Aq. 1M LiOH (15.0 mL, 15.0 mmol) was added to a sol. of compound C7 (2.04 g, 3.64 mmol) in THF (15 mL). The mixture was stirred at 60° C. for 3 days, and aq. 1M HCl was added. The mixture was extracted with EtOAc (2×). The combined org. extracts were washed with aq. 1M HCl and brine, dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (EtOAc) yielded the crude title compound mixed with 4-{4-[3-(2-chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-phenyl}-3,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester (600 mg, 30%). LC-MS: tR=1.08 min; ES+: 547.20.

Workup

  1. extractionThe mixture was extracted with EtOAc (2×)
  2. washextracts were washed with aq. 1M HCl and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customthe solvents were removed under reduced pressure
  6. customPurification of the crude by FC (EtOAc)

Sources & evidence

ORD record
ord-3e8610429d3c44afbd563daa9b8814a4
Source dataset
uspto-grants-2011_06
Patent number
US07968720B2

Reaction notes

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