(Diethylamino)sulfur trifluoride → Tert-butyl 4-(4-bromo-1,3-thiazol-2-yl)-4-fluoropiperidine-1-carboxylate

HRID 1051649Notes

Reaction equation

HRID 1051649 reaction equation
C(N(S(F)(F)[F:7])CC)C.[Br:10][C:11]1[N:12]=[C:13]([C:16]2(O)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[S:14][CH:15]=1>ClCCl>[Br:10][C:11]1[N:12]=[C:13]([C:16]2([F:7])[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[S:14][CH:15]=1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 66749307Tert-butyl 4-(4-bromo-1,3-thiazol-2-yl)-4-hydroxypiperidine-1-carboxylate

Product 1

HCID 66749859Tert-butyl 4-(4-bromo-1,3-thiazol-2-yl)-4-fluoropiperidine-1-carboxylateYield 78.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethylaminosulfur trifluoride (DAST) (0.083 mL, 0.627 mmol) was added to a 0° C. of tert-butyl 4-(4-bromothiazol-2-yl)-4-hydroxypiperidine-1-carboxylate (0.207 g, 0.570 mmol) in dichloromethane (2.8 mL). After 5 minutes, the cooling bath was removed and the reaction mixture was allowed to stir at room temperature overnight. Saturated aqueous sodium bicarbonate solution was added, and the aqueous phase was separated and extracted with dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 5-50% ethyl acetate-hexane) to afford tert-butyl 4-(4-bromothiazol-2-yl)-4-fluoropiperidine-1-carboxylate (0.163 g, 78%) as a colorless, waxy solid. MS (ESI, pos. ion) m/z 387, 389 [M+Na]+.

Workup

  1. customthe cooling bath was removed
  2. additionSaturated aqueous sodium bicarbonate solution was added
  3. customthe aqueous phase was separated
  4. extractionextracted with dichloromethane
  5. dry with materialThe combined organic phases were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 5-50% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-d738c4c4d31f4808ac0dc501c449f31e
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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