N-bromobutanimide → HCID 90220120, compound

HRID 2199778Notes

Reaction equation

HRID 2199778 reaction equation
[C:1]([O:5][C:6](=[O:21])[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]2[S:15][CH:16]=[C:17]([C:19]#[N:20])[N:18]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[Br:22]N1C(=O)CCC1=O>CN(C)C=O>[C:1]([O:5][C:6](=[O:21])[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]2[S:15][C:16]([Br:22])=[C:17]([C:19]#[N:20])[N:18]=2)[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 118556245HCID 118556245, compound

Product 1

HCID 90220120HCID 90220120, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of [(R)-1-(4-cyano-thiazol-2-yl)-piperidin-3-yl]-carbamic acid tert-butyl ester (13.0 g, 42.2 mmol) in N,N-dimethylformamide (250 mL) was added N-bromosuccinimide (8.25 g, 46. mmol) and the mixture was stirred under argon at ambient temperature for 30 minutes. Analysis by thin layer chromatography (silica stationary phase eluted with 25% v/v ethyl acetate in hexanes) indicated clean conversion of [(R)-1-(4-cyano-thiazol-2-yl)-piperidin-3-yl]-carbamic acid tert-butyl ester in to a slightly less polar compound. The reaction mixture was poured into water (1 L) and extracted with ethyl acetate (3×250 mL), the combined organic extracts were washed with brine (2×200 mL), dried over sodium sulfate, filtered and concentrated in vacuo to give an off-white solid. The crude product was triturated with 1:1 v/v diethyl ether/petroleum ether (300 mL total volume). [(R)-1-(5-Bromo-4-cyano-thiazol-2-yl)-piperidin-3-yl]-carbamic acid tert-butyl ester was obtained as a colorless solid by filtration, washing with 1:2 v/v diethyl ether/petroleum ether and drying by passage of air (14.33 g, 88%). An additional amount of [(R)-1-(5-bromo-4-cyano-thiazol-2-yl)-piperidin-3-yl]-carbamic acid tert-butyl ester was obtained by purification of the residue obtained from concentration of the mother liquors by chromatography using a silica gel column gradient eluted from 5% up to 40% v/v ethyl acetate in hexanes. The product containing fractions were combined and concentrated in vacuo to obtain additional [(R)-1-(5-bromo-4-cyano-thiazol-2-yl)-piperidin-3-yl]-carbamic acid tert-butyl ester as a colorless solid (1.18 g, 7%).

Workup

  1. washAnalysis by thin layer chromatography (silica stationary phase eluted with 25% v/v ethyl acetate in hexanes)
  2. additionThe reaction mixture was poured into water (1 L)
  3. extractionextracted with ethyl acetate (3×250 mL)
  4. washthe combined organic extracts were washed with brine (2×200 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give an off-white solid
  9. customThe crude product was triturated with 1:1 v/v diethyl ether/petroleum ether (300 mL total volume)

Sources & evidence

ORD record
ord-c3a7d0b5af6b4069a3fbfb765199552f
Source dataset
uspto-grants-2016_06
Patent number
US09359345B2

Reaction notes

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