Triethylamine → (RS)-(4-cyano-phenylamino)-{5-ethoxy-2-fluoro-3-[1-(2-hydroxy-ethyl)-piperidin-4-yloxy]-phenyl}acetic acid ethyl ester

HRID 478970Notes

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.Br[CH2:41][CH2:42][OH:43]>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[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]([CH2:41][CH2:42][OH:43])[CH2:20][CH2:21]2)[C:7]=1[F:22])[CH3:2]

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 300 mg (RS)-(4-cyano-phenylamino)-[5-ethoxy-2-fluoro-3-(piperidin-4-yloxy)-phenyl]-acetic acid ethyl ester described in example 11.2 in 10 ml THF was treated with 0.19 ml triethylamine, 0.82 ml 2-bromoethanol and 25 mg tetrabutylammonium iodide. The reaction mixture was heated to 50° C. for 6 hrs, then evaporated. The residue was taken up in water and extracted with EtOAc. The crude product was purified by chromatography on silica with dichloromethane/MeOH 9:1 to give 175 mg (RS)-(4-cyano-phenylamino)-{5-ethoxy-2-fluoro-3-[1-(2-hydroxy-ethyl)-piperidin-4-yloxy]-phenyl}acetic acid ethyl ester. MS: 486.4 ([M+H]+).

Workup

customevaporated
extractionextracted with EtOAc
customThe crude product was purified by chromatography on silica with dichloromethane/MeOH 9:1

Sources & evidence

ORD record: ord-aec52b78977f4b7fa0ec43b14eb95488
Source dataset: uspto-grants-2003_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06642386B2

Reaction notes

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