Ethanol → Ethyl 5-bromo-4-methylnicotinate

HRID 2277651Notes

Reaction equation

HRID 2277651 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:10]=1[CH3:11])[C:7]([OH:9])=[O:8].[CH2:12](O)[CH3:13].CCN=C=NCCCN(C)C.OP([O-])(O)=O.[K+]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:10]=1[CH3:11])[C:7]([O:9][CH2:12][CH3:13])=[O:8]

Participants

7

Reactant 4

HCID 702EthanolHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 516951Monobasic potassium phosphateHCID 70606755-Bromo-4-methylnicotinic acid

Product 1

HCID 86679924Ethyl 5-bromo-4-methylnicotinateYield 84%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred light brown suspension of 5-bromo-4-methylnicotinic acid (10.00 g, 46.3 mmol) and ethanol (2.97 mL) in DCM (231 mL) at 0° C. under argon was added EDCI (10.9 g, 55.5 mmol) and DMAP (566 mg, 4.63 mmol); stirring was continued overnight and the reaction mixture was allowed to warm up to room temperature. The reaction mixture was then poured on aq. 10% KH2PO4 solution followed by extraction with AcOEt (3×). The organic phases were washed once with aq. 10% KH2PO4, with sat. NaHCO3 and with aq. sat. NaCl solution. The combined organic phases were dried (Na2SO4), filtered and evaporated to afford the title compound (9.49 g, 84%) as brown solid. MS: 244.0 (M+H+, 1Br).

Workup

  1. extractionfollowed by extraction with AcOEt (3×)
  2. washThe organic phases were washed once with aq. 10% KH2PO4, with sat. NaHCO3 and with aq. sat. NaCl solution
  3. dry with materialThe combined organic phases were dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated

Sources & evidence

ORD record
ord-6c86513e8ad8443fa09aed52aab7a698
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

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