Sodium hydride → 2-(1-Cyclobutyl-piperidin-4-yloxy)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid tert-butyl ester

HRID 1402668Notes

Reaction equation

HRID 1402668 reaction equation
[CH:1]1([N:5]2[CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][C:24]2[N:27]=[C:28](Br)[S:29][C:23]=2[CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]>O1CCCC1>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][C:24]2[N:27]=[C:28]([O:11][CH:8]3[CH2:7][CH2:6][N:5]([CH:1]4[CH2:4][CH2:3][CH2:2]4)[CH2:10][CH2:9]3)[S:29][C:23]=2[CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 111629512-Bromo-4,5,6,7-tetrahydro(1,3)thiazolo(5,4-c)pyridine, N-BOC protectedHCID 581554161-Cyclobutylpiperidin-4-ol

Product 1

HCID 666112882-(1-Cyclobutyl-piperidin-4-yloxy)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid tert-butyl esterYield 56.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

1-Cyclobutyl-piperidin-4-ol (1.6 grams, 10 mmol) in tetrahydrofuran (20 mL) was treated with cooled and stirred suspension of sodium hydride (0.9 grams, 18 mmol) in tetrahydrofuran (20 mL) slowly over a period of 30 minutes; the reaction mixture was stirred for 1 hour. A solution of 2-Bromo-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid tert-butyl ester (3 grams, 9 mmol, obtained in preparation 1) in tetrahydrofuran (30 mL) was added drop wise over a period of 15 minutes and refluxed the reaction for 6 hours. Reaction mass was quenched with ice cold water and the product was extracted with ethyl acetate (3×50 mL). Combined organics were washed with water followed by brine and dried over anhydrous sodium sulphate. Organic volatiles were evaporated under vacuum. The residue was purified by flash chromatography (ethylacetate/n-hexane, 1/1) to obtain the title compound (2.0 grams).

Workup

  1. temperaturewith cooled
  2. stirringthe reaction mixture was stirred for 1 hour
  3. temperaturerefluxed
  4. customthe reaction for 6 hours
  5. customReaction mass
  6. customwas quenched with ice cold water
  7. extractionthe product was extracted with ethyl acetate (3×50 mL)
  8. washCombined organics were washed with water
  9. dry with materialdried over anhydrous sodium sulphate
  10. customOrganic volatiles were evaporated under vacuum
  11. customThe residue was purified by flash chromatography (ethylacetate/n-hexane, 1/1)

Sources & evidence

ORD record
ord-075959bef833424c82a50995bad10245
Source dataset
uspto-grants-2014_12
Patent number
US08912179B2

Reaction notes

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