Hydrochloric Acid → 2-(1-{[3,5-Bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazole-4-carboxylic acid

HRID 1047321Notes

Reaction equation

HRID 1047321 reaction equation
[F:1][CH:2]([F:30])[C:3]1[CH:7]=[C:6]([CH:8]([F:10])[F:9])[N:5]([CH2:11][C:12]([N:14]2[CH2:19][CH2:18][CH:17]([C:20]3[S:21][CH:22]=[C:23]([C:25]([O:27]CC)=[O:26])[N:24]=3)[CH2:16][CH2:15]2)=[O:13])[N:4]=1.Cl>O1CCCC1.O>[F:30][CH:2]([F:1])[C:3]1[CH:7]=[C:6]([CH:8]([F:9])[F:10])[N:5]([CH2:11][C:12]([N:14]2[CH2:19][CH2:18][CH:17]([C:20]3[S:21][CH:22]=[C:23]([C:25]([OH:27])=[O:26])[N:24]=3)[CH2:16][CH2:15]2)=[O:13])[N:4]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 58242750HCID 58242750, compound

Product 1

HCID 444691842-(1-{[3,5-Bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazole-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazole-4-carboxylate (IV-1, 13.3 g) is dissolved in tetrahydrofuran (80 ml). LiOH monohydrate (1.86 g) dissolved in water (20 ml) is then added. After 3 hours, water is added, the pH is adjusted to 2-3 with dilute hydrochloric acid (1M), the mixture is then extracted with ethyl acetate and the combined organic phases are dried with sodium sulfate. The solid is filtered off and the solvent is removed by distillation. This gives 2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazole-4-carboxylic acid (11.7 g, 94%).

Workup

  1. additionis then added
  2. extractionthe mixture is then extracted with ethyl acetate
  3. dry with materialthe combined organic phases are dried with sodium sulfate
  4. filtrationThe solid is filtered off
  5. customthe solvent is removed by distillation

Sources & evidence

ORD record
ord-70571fbf0ec5413a9969f3cf7234a86c
Source dataset
uspto-grants-2013_10
Patent number
US08569509B2

Reaction notes

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