Dichloromethane → HCID 66749126, compound

HRID 2401858Notes

Reaction equation

HRID 2401858 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[N:8][C:7]=1[CH3:17])=[O:5])[CH3:2].C(Cl)Cl.[Br:21]N1C(=O)CCC1=O>N(C(C)(C)C#N)=NC(C)(C)C#N>[Br:21][CH2:17][C:7]1[N:8]=[C:9]([N:11]2[CH2:12][CH2:13][O:14][CH2:15][CH2:16]2)[S:10][C:6]=1[C:4]([O:3][CH2:1][CH3:2])=[O:5]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 67184N-bromobutanimideHCID 12263412HCID 12263412, compound

Product 1

HCID 66749126HCID 66749126, compoundYield 71.2%

Reagents, catalysts & solvents 1

HCID 6547AzobisisobutyronitrileCatalyst

Procedure

To a round bottom flask containing a solution of ethyl-4-methyl-2-(morpholin-4-yl)-1,3-thiazole-5-carboxylate (14.50 g, 56.57 mmol) in methylene chloride (400 mL, 6000 mmol) were added N-bromosuccinimide (10.07 g, 56.57 mmol) and 2,2′-azo-bis-isobutyronitrile (464 mg, 2.83 mmol). The mixture was stirred at reflux overnight. Reaction was quenched via addition of 10% aqueous sodium bisulfite (20 g in 200 ml water) and stirred for 20 minutes. Mixture was transferred to a separatory funnel, the layers separated, and the aqueous layer was extracted 2×DCM. Combined organic layers were dried with Na2SO4, filtered, and concentrated in vacuo. The resulting residue was dissolved in DCM and adsorbed onto silica gel. Purification via column chromatography (220 g Isco column, gradient elution 0-10% EtOAc in 1:1 DCM:hexanes) afforded ethyl 4-(bromomethyl)-2-(morpholin-4-yl)-1,3-thiazole-5-carboxylate (13.5 g, yield 71.1%). LC/MS: (FA) ES+ 335, 337; 1H NMR (300 MHz, CDCl3) δ 4.76 (s, 2H), 4.30 (dd, J=7.1, 7.1, 2H), 3.88-3.72 (m, 4H), 3.62-3.49 (m, 4H), 1.35 (dd, J=7.1, 7.1, 3H).

Workup

  1. temperatureat reflux overnight
  2. customReaction
  3. customwas quenched via addition of 10% aqueous sodium bisulfite (20 g in 200 ml water)
  4. stirringstirred for 20 minutes
  5. customMixture was transferred to a separatory funnel
  6. customthe layers separated
  7. extractionthe aqueous layer was extracted 2×DCM
  8. dry with materialCombined organic layers were dried with Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. dissolutionThe resulting residue was dissolved in DCM
  12. customPurification
  13. washvia column chromatography (220 g Isco column, gradient elution 0-10% EtOAc in 1:1 DCM:hexanes)

Sources & evidence

ORD record
ord-5c88093ce52949268c8b95698aea3aca
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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