Acetic Acid → 5-(3-((3R)-3-((E)-3-Hydroxy-4-(3-(trifluoromethyl)phenyl)but-1-en-1-yl)-1,1-dioxidoisothiazolidin-2-yl)propyl)thiophene-2-carboxylic acid

HRID 524367Notes

Reaction equation

HRID 524367 reaction equation
[OH-].[Li+].[OH:3][CH:4]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=1)/[CH:5]=[CH:6]/[C@H:7]1[CH2:11][CH2:10][S:9](=[O:13])(=[O:12])[N:8]1[CH2:14][CH2:15][CH2:16][C:17]1[S:21][C:20]([C:22]([O:24]C)=[O:23])=[CH:19][CH:18]=1.C(O)(=O)C>O.C1COCC1>[OH:3][CH:4]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:34])([F:35])[F:36])[CH:28]=1)/[CH:5]=[CH:6]/[C@H:7]1[CH2:11][CH2:10][S:9](=[O:12])(=[O:13])[N:8]1[CH2:14][CH2:15][CH2:16][C:17]1[S:21][C:20]([C:22]([OH:24])=[O:23])=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 3939Lithium HydroxideHCID 118677369Methyl 5-(3-((3R)-3-((E)-3-hydroxy-4-(3-(trifluoromethyl)phenyl)but-1-en-1-yl)-1,1-dioxidoisothiazolidin-2-yl)propyl)thiophene-2-carboxylate

Product 1

HCID 1186773605-(3-((3R)-3-((E)-3-Hydroxy-4-(3-(trifluoromethyl)phenyl)but-1-en-1-yl)-1,1-dioxidoisothiazolidin-2-yl)propyl)thiophene-2-carboxylic acidYield 41.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Lithium hydroxide (0.25 mL of a 0.5N solution in H2O, 0.125 mmol) was added to a solution of the ester 13 (25 mg, 0.048 mmol) in THF (1.0 mL) at 23° C. The reaction mixture was stirred for 16 h, acidified with acetic acid and extracted with EtOAc. The organic portion was washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography (silica gel, 10% MeOH/CH2Cl2) afforded 10 mg (41%) of pure carboxylic acid 14.

Workup

  1. extractionextracted with EtOAc
  2. washThe organic portion was washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by flash column chromatography (silica gel, 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-a19cfea4aef844e8b01c8a252580482c
Source dataset
uspto-grants-2016_05
Patent number
US09340534B2

Reaction notes

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