tert-Butanol → 1-[4-(Pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperidine-4-carboxylic acid

HRID 907537

Reaction equation

HRID 907537 reaction equation
Cl[C:2]1[C:3]([N:7]2[CH2:12][CH2:11][CH:10]([C:13]([OH:15])=[O:14])[CH2:9][CH2:8]2)=[N:4][S:5][N:6]=1.[N:16]1[CH:21]=[CH:20][C:19]([CH2:22][OH:23])=[CH:18][CH:17]=1.C(C(CCC)[O-])(C)(C)C.[K+].C(O)(C)(C)C>O>[N:16]1[CH:21]=[CH:20][C:19]([CH2:22][O:23][C:2]2[C:3]([N:7]3[CH2:12][CH2:11][CH:10]([C:13]([OH:15])=[O:14])[CH2:9][CH2:8]3)=[N:4][S:5][N:6]=2)=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 114724-HydroxymethylpyridineHCID 23710422Potassium tert-butylbutoxideHCID 590139601-(4-Chloro-[1,2,5]thiadiazol-3-yl)-piperidine-4-carboxylic acid

Product 1

HCID 590139171-[4-(Pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperidine-4-carboxylic acidYield 59%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

1-(4-Chloro-[1,2,5]thiadiazol-3-yl)-piperidine-4-carboxylic acid (7.99 g, 32 mmol), pyridin-4-yl-methanol (7.39 g, 68 mmol) and a solution of 1M potassium tert-butyl butoxide in tert-butyl alcohol (100 mL, 100 mmol) were combined and stirred at room temperature overnight. The reaction mixture is diluted with H2O (500 mL) and washed with EtOAc (3×). The aqueous phase is concentrated to ˜250 mL and acidified to pH 5-6 with conc'd HCl. The resulting solids are filtered, washed with H2O and dried under high vacuum to give 6.04 g (59%) of 1-[4-(pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperidine-4-carboxylic acid. 1H NMR (DMSO-d6) 8.57 (d, 2H), 7.41 (d, 2H), 5.51 (s, 2H), 4.03 (m, 2H), 3.00 (m, 2H), 2.46 (m, 1H), 1.91 (m, 2H), 1.63 (m, 2H) ppm. LC-MS (M−)=319.

Workup

  1. washwashed with EtOAc (3×)
  2. concentrationThe aqueous phase is concentrated to ˜250 mL
  3. filtrationThe resulting solids are filtered
  4. washwashed with H2O
  5. customdried under high vacuum

Sources & evidence

ORD record
ord-de0d6ce593cd4f23b464015b68b90e6b
Source dataset
uspto-grants-2011_09
Patent number
US08013156B2

Linked notes

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