Hydrochloric Acid → (Rac)-3-fluoro-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid

HRID 2402390Notes

Reaction equation

HRID 2402390 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1[C:10]([C:43]([O:45]C)=[O:44])=[CH:11][C:12]2[CH2:13][CH2:14][CH2:15][C:16]([OH:42])([C:19]3[S:20][C:21]([C:24]4[CH:29]=[C:28]([CH3:30])[CH:27]=[C:26]([NH:31][C:32]5[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[CH:34][N:33]=5)[N:25]=4)=[CH:22][N:23]=3)[C:17]=2[CH:18]=1.[OH-].[K+].Cl>O1CCCC1>[F:8][C:9]1[C:10]([C:43]([OH:45])=[O:44])=[CH:11][C:12]2[CH2:13][CH2:14][CH2:15][C:16]([OH:42])([C:19]3[S:20][C:21]([C:24]4[CH:29]=[C:28]([CH3:30])[CH:27]=[C:26]([NH:31][C:32]5[CH:37]=[C:36]([C:38]([F:41])([F:39])[F:40])[CH:35]=[CH:34][N:33]=5)[N:25]=4)=[CH:22][N:23]=3)[C:17]=2[CH:18]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 131731735HCID 131731735, compound

Product 1

HCID 70978010(Rac)-3-fluoro-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acidYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 3-fluoro-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate, trifluoroacetate salt (200 mg, 0.297 mmol) in tetrahydrofuran (1.2 mL) under argon was added potassium hydroxide (40% aqueous solution, 834 μl, 5.95 mmol), and the reaction was stirred at rt for 16 h. The pH was adjusted to 5 by the addition of aqueous HCl (2.0 M). The resulting mixture was extracted with ethyl acetate (3 times), and the combined organic phases were dried (Na2SO4) and concentrated under reduced pressure to afford (rac)-3-fluoro-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid (115.0 mg, 0.211 mmol, 71% yield) as a light yellow solid. MS ESI calcd for C26H20F4N4O3S [M+H]+ 545, found 545.

Workup

  1. extractionThe resulting mixture was extracted with ethyl acetate (3 times)
  2. dry with materialthe combined organic phases were dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ebe0fc22d26746f7bf4e248d25d7620d
Source dataset
uspto-grants-2014_08
Patent number
US08796310B2

Reaction notes

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