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

HRID 478968Notes

Reaction equation

HRID 478968 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[C:19]([O:21][CH2:22][CH3:23])[CH:18]=[C:17]([CH:24]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([C:37]#[N:38])=[CH:33][CH:32]=3)[C:25]([O:27][CH2:28][CH3:29])=[O:26])[C:16]=2[F:39])[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.C([O-])([O-])=O.[Na+].[Na+]>ClCCl>[CH2:28]([O:27][C:25](=[O:26])[CH:24]([NH:30][C:31]1[CH:32]=[CH:33][C:34]([C:37]#[N:38])=[CH:35][CH:36]=1)[C:17]1[CH:18]=[C:19]([O:21][CH2:22][CH3:23])[CH:20]=[C:15]([O:14][CH:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)[C:16]=1[F:39])[CH3:29]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 69923731(RS)-4-{3-[(4-cyano-phenylamino)-ethoxycarbonyl-methyl]-5-ethoxy-2-fluoro-phenoxy}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 69923727(RS)-(4-cyano-phenylamino)-[5-ethoxy-2-fluoro-3-(piperidin-4-yloxy)-phenyl]-acetic acid ethyl esterYield 82.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 2.30 g (RS)-4-{3-[(4-cyano-phenylamino)-ethoxycarbonyl-methyl]-5-ethoxy-2-fluoro-phenoxy}-piperidine-1-carboxylic acid tert-butyl ester in 40 ml dichloromethane was cooled to 0° C. and treated dropwise with 3.25 ml trifluoroacetic acid. The reaction mixture was warmed to r.t. within 3 hrs, then again cooled to 0° C. and treated with 20 ml of 10% Na2CO3 solution. The product was extracted with dichloromethane. The organic layer was dried over MgSO4, filtrated and evaporated to give 1.55 g (RS)-(4-cyano-phenylamino)-[5-ethoxy-2-fluoro-3-(piperidin-4-yloxy)-phenyl]-acetic acid ethyl ester as an off-white solid foam which was used for the next step without further purification. MS: 442.3 ([M+H]+).

Workup

  1. temperatureagain cooled to 0° C.
  2. extractionThe product was extracted with dichloromethane
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltrated
  5. customevaporated

Sources & evidence

ORD record
ord-fa22104b219043bcb784410d51590ecb
Source dataset
uspto-grants-2003_11
Patent number
US06642386B2

Reaction notes

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