Water → 4-(5-chloro-2-fluorophenyl)-2-(3-hydroxyphenyl)-1-(2-methylalanyl)-2,5-dihydro-1H-pyrrole

HRID 1394926ノート

反応式

HRID 1394926 の反応式
[Si]([O:8][C:9]1[CH:10]=[C:11]([CH:15]2[CH:19]=[C:18]([C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=3[F:27])[CH2:17][N:16]2[C:28](=[O:40])[C:29]([NH:32]C(=O)OC(C)(C)C)([CH3:31])[CH3:30])[CH:12]=[CH:13][CH:14]=1)(C(C)(C)C)(C)C.FC(F)(F)C(O)=O.C(=O)([O-])[O-].[K+].[K+].O>ClCCl.CO>[Cl:26][C:24]1[CH:23]=[CH:22][C:21]([F:27])=[C:20]([C:18]2[CH2:17][N:16]([C:28](=[O:40])[C:29]([CH3:31])([CH3:30])[NH2:32])[CH:15]([C:11]3[CH:12]=[CH:13][CH:14]=[C:9]([OH:8])[CH:10]=3)[CH:19]=2)[CH:25]=1

参加物

7

反応物 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 59656598tert-butyl 2-[2-(3 {[tert-butyl(dimethyl)silyl]oxy}phenyl)-4-(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrol-1-yl]-1,1-dimethyl-2-oxoethylcarbamate

生成物 1

HCID 596566024-(5-chloro-2-fluorophenyl)-2-(3-hydroxyphenyl)-1-(2-methylalanyl)-2,5-dihydro-1H-pyrrole

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

A solution of tert-butyl 2-[2-(3 {[tert-butyl(dimethyl)silyl]oxy}phenyl)-4-(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrol-1-yl]-1,1-dimethyl-2-oxoethylcarbamate (17-3, 247 mg, 0.419 mmol, 1 equiv) and trifluoroacetic acid (4 mL) in dichloromethane (10 mL) was stirred under ambient conditions for 1 hour. The reaction was concentrated at 23° C. and the residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic layer was washed with brine, dried over magnesium sulfate and concentrated to yield a yellow gum. A solution of the gum in methanol (5 mL) was treated with potassium carbonate (290 mg, 2.10 mmol, 5.00 equiv) and water (1 mL). The reaction mixture was stirred under ambient conditions for 2 hours, then concentrated. The aqueous solution was acidified with aqueous 1 N HCl solution to pH 8 and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and concentrated to provide 4-(5-chloro-2-fluorophenyl)-2-(3-hydroxyphenyl)-1-(2-methylalanyl)-2,5-dihydro-1H-pyrrole (174) as a cream-colored solid. 1H NMR (500 MHz, CDCl3) δ 7.30 (dd, 1H, J=6.6, 2.7 Hz), 7.30 (m, 1H), 7.18 (t, 1H, J=7.8 Hz), 7.05 (t, 1H, J=9.2 Hz), 6.83 (br d, 1H, J=7.6 Hz), 6.78 (br s, 1H), 6.70 (dd, 1H, J=8.1, 1.8 Hz), 6.38 (s, 1H), 5.92 (br s, 1H), 5.30 (m, 1H), 5.08 (m, 1H), 1.46 (s, 6H). LRMS m/z (M+H) 375.0 found, 375.0 required.

後処理

  1. concentrationThe reaction was concentrated at 23° C.
  2. customthe residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customto yield a yellow gum
  7. concentrationconcentrated
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe organic layer was washed with brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated

出典と根拠

ORDレコード
ord-458d30585479419cb84570cf23c31c3e
出典データセット
uspto-grants-2008_03
特許番号
US07348440B2

反応ノート

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