Ethyl bromoacetate → (RS)-(4-cyano-phenylamino)-[5-ethoxy-3-(1-ethoxycarbonylmethyl-piperidin-4-yloxy)-2-fluoro-phenyl]-acetic acid ethyl ester

HRID 478969Notes

Reaction equation

HRID 478969 reaction equation
[CH2:1]([O:3][C:4](=[O:32])[CH:5]([NH:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[CH:26][CH:25]=1)[C:6]1[CH:11]=[C:10]([O:12][CH2:13][CH3:14])[CH:9]=[C:8]([O:15][CH:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[C:7]=1[F:22])[CH3:2].C(N(CC)CC)C.[CH2:40]([O:42][C:43](=[O:46])[CH2:44]Br)[CH3:41]>C1COCC1>[CH2:1]([O:3][C:4](=[O:32])[CH:5]([NH:23][C:24]1[CH:25]=[CH:26][C:27]([C:30]#[N:31])=[CH:28][CH:29]=1)[C:6]1[CH:11]=[C:10]([O:12][CH2:13][CH3:14])[CH:9]=[C:8]([O:15][CH:16]2[CH2:17][CH2:18][N:19]([CH2:44][C:43]([O:42][CH2:40][CH3:41])=[O:46])[CH2:20][CH2:21]2)[C:7]=1[F:22])[CH3:2]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 8471TriethylamineHCID 69923727(RS)-(4-cyano-phenylamino)-[5-ethoxy-2-fluoro-3-(piperidin-4-yloxy)-phenyl]-acetic acid ethyl ester

Product 1

HCID 69923157(RS)-(4-cyano-phenylamino)-[5-ethoxy-3-(1-ethoxycarbonylmethyl-piperidin-4-yloxy)-2-fluoro-phenyl]-acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 300 mg (RS)-(4-cyano-phenylamino)-[5-ethoxy-2-fluoro-3-(piperidin-4-yloxy)-phenyl]-acetic acid ethyl ester in 10 ml THF was cooled to 0° C. and treated with 0.14 ml triethylamine and 0.90 ml bromoacetic acid ethyl ester. The reaction mixture was stirred at r.t. overnight, then evaporated. The residue was taken up in water and extracted with EtOAc. The organic layer was dried over MgSO4. The crude product was purified by chromatography on silica with cyclohexane/EtOAc 1:2 to give 215 mg (RS)-(4-cyano-phenylamino)-[5-ethoxy-3-(1-ethoxycarbonylmethyl-piperidin-4-yloxy)-2-fluoro-phenyl]-acetic acid ethyl ester as a colorless foam. MS: 528.3 ([M+H]+).

Workup

  1. customevaporated
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried over MgSO4
  4. customThe crude product was purified by chromatography on silica with cyclohexane/EtOAc 1:2

Sources & evidence

ORD record
ord-f2e063ccbf1f445eb8acf2b0fc86406c
Source dataset
uspto-grants-2003_11
Patent number
US06642386B2

Reaction notes

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