Ethanol → Ethyl 5-bromo-4-methylnicotinate

HRID 530319Notes

Reaction equation

HRID 530319 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 (2.35 g, 2.97 mL, 50.9 mmol) in CH2Cl2 (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 over night and the reaction mixture was allowed to warm up to RT. The reaction mixture was poured on aq. 10% KH2PO4 solution followed by extraction with AcOEt (3×). The organic phases were washed once with aq. 10% KH2PO4, aq. 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. waitwas continued over night
  2. extractionfollowed by extraction with AcOEt (3×)
  3. washThe organic phases were washed once with aq. 10% KH2PO4, aq. sat. NaHCO3 and with aq. sat. NaCl solution
  4. dry with materialThe combined organic phases were dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-a3a7cbfc4afd44ea9aa0c84d2b8a0aca
Source dataset
uspto-grants-2016_05
Patent number
US09353081B2

Reaction notes

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