Dimethylformamide → 5-Bromo-2-(cis-2,6-dimethyl-morpholin-4-yl)-thiazole-4-carbonitrile

HRID 473976Notes

Reaction equation

HRID 473976 reaction equation
[CH3:1][C@H:2]1[O:7][C@@H:6]([CH3:8])[CH2:5][N:4]([C:9]2[S:10][CH:11]=[C:12]([C:14]#[N:15])[N:13]=2)[CH2:3]1.CN(C=O)C.[Br:21]N1C(=O)CCC1=O.[OH-].[Na+]>O>[Br:21][C:11]1[S:10][C:9]([N:4]2[CH2:3][C@H:2]([CH3:1])[O:7][C@H:6]([CH3:8])[CH2:5]2)=[N:13][C:12]=1[C:14]#[N:15]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 67184N-bromobutanimideHCID 672160172-(cis-2,6-Dimethyl-morpholin-4-yl)-thiazole-4-carbonitrile

Product 1

HCID 672167795-Bromo-2-(cis-2,6-dimethyl-morpholin-4-yl)-thiazole-4-carbonitrileYield 73.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A flask charged with Intermediate 2 (25.61 g, 114.69 mmol) and DMF (250 mL) was cooled in an ice/water bath. N-bromosuccinimide (24.49 g, 137.63 mmol) was added portionwise (slightly exothermic reaction). The reaction mixture was stirred at room temperature for 10 min. Water (400 mL) was then added dropwise leading to a yellow precipitate, followed by sodium hydroxide 1 M (115 mL). The precipitate was filtered, washed with water (50 mL) and DIPE (10 mL). This solid was recrystallised from acetonitrile. Filtration and overnight drying in a vacuum oven at 50° C. yielded 25.5 g (73%) of Intermediate 3 as a yellow solid.

Workup

  1. temperaturewas cooled in an ice/water bath
  2. customslightly exothermic reaction)
  3. filtrationThe precipitate was filtered
  4. washwashed with water (50 mL) and DIPE (10 mL)
  5. customThis solid was recrystallised from acetonitrile
  6. filtrationFiltration and overnight
  7. customdrying in a vacuum oven at 50° C.

Sources & evidence

ORD record
ord-f42092a3c7fd4193b1bc3f7daeadf0af
Source dataset
uspto-grants-2014_01
Patent number
US08637510B2

Reaction notes

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