Hydrochloric Acid → 3-(4-Bromophenyl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)propanoic acid

HRID 1712766ノート

反応式

HRID 1712766 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[C:30]([C:35]([F:38])([F:37])[F:36])[CH:29]=2)([C:14]2[CH:19]=[C:18]([O:20][C:21]([F:26])([F:25])[CH:22]([F:24])[F:23])[CH:17]=[C:16]([F:27])[CH:15]=2)[C:10]([O:12]C)=[O:11])=[CH:4][CH:3]=1.C1COCC1.[Li+].[OH-].Cl>CO>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[C:30]([C:35]([F:38])([F:37])[F:36])[CH:29]=2)([C:14]2[CH:19]=[C:18]([O:20][C:21]([F:26])([F:25])[CH:22]([F:24])[F:23])[CH:17]=[C:16]([F:27])[CH:15]=2)[C:10]([OH:12])=[O:11])=[CH:6][CH:7]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 86613055Methyl 3-(4-bromophenyl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)propanoate

生成物 1

HCID 594587593-(4-Bromophenyl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)propanoic acid収率 81%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

A mixture of methyl 3-(4-bromophenyl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)propanoate (865 mg, 1.34 mmol) in MeOH (10 mL)/THF (20 mL) and LiOH (2 N, 10 mL) was stirred at rt overnight. The reaction mixture was made acidic by addition of 1 N HCl to pH=1-2 and concentrated. The resulting residue was partitioned between EtOAc and sat. NaCl. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by ISCO (40 g siligel column, 0-10% MeOH/DCM over 30 min) to yield 3-(4-bromophenyl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)propanoic acid as a colorless oil (650 mg, 81% yield). LCMS: RT=2.17 min [M+H] 600.88 (Phenomenex Luna C18 4.6×30 mm column, eluting with 10-90% MeOH/H2O containing 0.% TFA, 2 min gradient, flow rate 5 mL/min, wavelength 220 nm); HPLC: RT=4.45 min (Phenomenex Luna C18 4.6×50 mm column, eluting with 10-90% MeOH/H2O containing 0.2% PPA, flow rate 4 mL/min, wavelength 220 nm).

後処理

  1. concentrationconcentrated
  2. customThe resulting residue was partitioned between EtOAc and sat. NaCl
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by ISCO (40 g siligel column, 0-10% MeOH/DCM over 30 min)

出典と根拠

ORDレコード
ord-2e6d56477aaf4e2ba3b32543f260e69f
出典データセット
uspto-grants-2010_09
特許番号
US07790770B2

反応ノート

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