Hydrochloric Acid → 2-(4,4-Difluoropiperidin-1-yl)benzo[d]thiazole-6-carboxylic acid

HRID 1023102Notes

Reaction equation

HRID 1023102 reaction equation
BrC1SC2C=C(C(OCC)=O)C=CC=2N=1.FC1(F)CCNCC1.C([O-])([O-])=O.[Cs+].[Cs+].[F:30][C:31]1([F:51])[CH2:36][CH2:35][N:34]([C:37]2[S:38][C:39]3[CH:45]=[C:44]([C:46]([O:48]CC)=[O:47])[CH:43]=[CH:42][C:40]=3[N:41]=2)[CH2:33][CH2:32]1.Cl>CC#N.O>[F:51][C:31]1([F:30])[CH2:36][CH2:35][N:34]([C:37]2[S:38][C:39]3[CH:45]=[C:44]([C:46]([OH:48])=[O:47])[CH:43]=[CH:42][C:40]=3[N:41]=2)[CH2:33][CH2:32]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 27583524,4-DifluoropiperidineHCID 12067225Ethyl 2-bromo-6-benzothiazolecarboxylateHCID 59625687HCID 59625687, compound

Product 1

HCID 596259162-(4,4-Difluoropiperidin-1-yl)benzo[d]thiazole-6-carboxylic acidYield 99%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of ethyl 2-bromo-benzo[d]thiazole-6-carboxylate 49a (1.75 mmol, 500 mg), 4,4-difluoropiperidine 49b (1.92 mmol, 303 mg), and Cs2CO3 (5.24 mmol, 1.71 g) in 15 mL of CH3CN was refluxed overnight. The suspension was cooled to room temperature and 15 mL of water was added to the mixture (containing ethyl 2-(4,4-difluoropiperidin-1-yl)benzo[d]thiazole-6-carboxylate 49c). The reaction mixture was heated at 60° C. for 18 h. After cooling, the mixture was acidified using 3N aqueous HCl and the resulting precipitate was filtered to give 575 mg (99%) of 49d. MS m/z (M+H+) 299.1.

Workup

  1. temperaturewas refluxed overnight
  2. temperatureThe reaction mixture was heated at 60° C. for 18 h
  3. temperatureAfter cooling
  4. filtrationthe resulting precipitate was filtered

Sources & evidence

ORD record
ord-9836a28af38c484ebccdcc6e6705c9d0
Source dataset
uspto-grants-2014_05
Patent number
US08722658B2

Reaction notes

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