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

HRID 2428202Notes

Reaction equation

HRID 2428202 reaction equation
C[O:2][C:3]([C:5]1[CH2:6][N:7]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:8][CH2:9][C:10]=1[C:11]1[CH:12]=[N:13][C:14]([O:17][CH2:18][C:19]2[O:23][N:22]=[C:21]([C:24]3[C:29]([F:30])=[CH:28][CH:27]=[C:26]([F:31])[C:25]=3[Cl:32])[CH:20]=2)=[CH:15][CH:16]=1)=[O:4].[Li+].[OH-].Cl>C1COCC1>[C:36]([O:35][C:33]([N:7]1[CH2:8][CH2:9][C:10]([C:11]2[CH:12]=[N:13][C:14]([O:17][CH2:18][C:19]3[O:23][N:22]=[C:21]([C:24]4[C:29]([F:30])=[CH:28][CH:27]=[C:26]([F:31])[C:25]=4[Cl:32])[CH:20]=3)=[CH:15][CH:16]=2)=[C:5]([C:3]([OH:4])=[O:2])[CH2:6]1)=[O:34])([CH3:39])([CH3:37])[CH3:38]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 671489026-[3-(2-Chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-5',6'-dihydro-2'H-[3,4']bipyridinyl-1',3'-dicarboxylic Acid 1'-tert-butyl Ester 3'-methyl Ester

Product 1

HCID 671489016-[3-(2-Chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-5',6'-dihydro-2'H-[3,4']bipyridinyl-1',3'-dicarboxylic Acid 1'-tert-butyl Ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of compound C8 (1.00 g, 1.78 mmol) and aq. 1M LiOH (7.00 mL, 7.00 mmol) in THF (7.00 mL) was stirred overnight at 70° C. Aq. 1M HCl was added until a pH=4 was reached. The mixture was extracted with EtOAc (3×). The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Drying the residue under high vacuum yielded the title compound mixed with 6-[3-(2-chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-3′,6′-dihydro-2′H-[3,4′]bipyridinyl-1′,3′-dicarboxylic acid 1′-tert-butyl ester (976 mg, quantitative yield) that was used further without purification. LC-MS: tR=1.06 min; ES+: 548.30.

Workup

  1. extractionThe mixture was extracted with EtOAc (3×)
  2. dry with materialextracts were dried over MgSO4
  3. filtrationfiltered
  4. customthe solvents were removed under reduced pressure
  5. customDrying the residue under high vacuum

Sources & evidence

ORD record
ord-22ac679b4db84469b33fef7cc8b3c796
Source dataset
uspto-grants-2011_06
Patent number
US07968720B2

Reaction notes

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