Hydrochloric Acid → (S)-4-(1-(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)butyl)benzoic acid tromethamine salt

HRID 1892745ノート

反応式

HRID 1892745 の反応式
[CH3:1][C:2]1[CH:3]=[C:4]([CH:20]=[C:21]([CH3:32])[C:22]=1[N:23]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[N:24]1)[O:5][C@H:6]([C:10]1[CH:19]=[CH:18][C:13]([C:14]([O:16]C)=[O:15])=[CH:12][CH:11]=1)[CH2:7][CH2:8][CH3:9].[OH-].[Na+].Cl.[CH2:36]([OH:43])[C:37]([NH2:42])([CH2:40][OH:41])[CH2:38][OH:39]>O.CO>[NH2:42][C:37]([CH2:40][OH:41])([CH2:38][OH:39])[CH2:36][OH:43].[CH3:1][C:2]1[CH:3]=[C:4]([CH:20]=[C:21]([CH3:32])[C:22]=1[N:23]1[CH:27]=[C:26]([C:28]([F:29])([F:31])[F:30])[CH:25]=[N:24]1)[O:5][C@H:6]([C:10]1[CH:11]=[CH:12][C:13]([C:14]([OH:16])=[O:15])=[CH:18][CH:19]=1)[CH2:7][CH2:8][CH3:9]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 6503Tris(hydroxymethyl)aminomethaneHCID 14798Sodium HydroxideHCID 68156304(S)-methyl 4-(1-(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)butyl)benzoate

生成物 1

HCID 68157375(S)-4-(1-(3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)butyl)benzoic acid tromethamine salt収率 77%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 962Water溶媒

反応条件

温度
35 °C

実験手順

To the solution from step 3 was added 5 M sodium hydroxide solution (29 mL, 145 mmol) and methanol (30 mL). The solution was heated to 35° C. for 6 h. After cooling to room temperature, the solution was acidified with conc. HCl (12.4 mL). The reaction was washed with water (30 mL). The organic solution was concentrated and the residue taken up in acetonitrile (100 mL). A solution of tris(hydroxymethyl)aminomethane (5.82 g, 48 mmol) in water (5 mL) was added slowly. The resulting slurry was cooled to 0° C. The product was filtered and washed with acetonitrile to give the desired salt as a white solid (20.5 g, 77% yield) 1H NMR (400 MHz, DMSO-d6) δ: 8.53 (s, 1H), 8.09 (s, 1H), 7.80 (d, J=8.2 Hz, 2H), 7.35 (d, J=8.2 Hz, 2H), 6.74 (s, 2H), 5.38 (dd, J=7.4, 5.1 Hz, 1H), 3.37 (s, 6H), 1.94-1.85 (m, 1H), 1.79 (s, 6H), 1.76-1.68 (m, 1H), 1.45-1.29 (m, 2H), 0.89 (t, J=7.5 Hz, 3H).

後処理

  1. temperatureAfter cooling to room temperature
  2. washThe reaction was washed with water (30 mL)
  3. concentrationThe organic solution was concentrated
  4. temperatureThe resulting slurry was cooled to 0° C
  5. filtrationThe product was filtered
  6. washwashed with acetonitrile

出典と根拠

ORDレコード
ord-a857422c079f4385b1a07201bf32425b
出典データセット
uspto-grants-2013_08
特許番号
US08507533B2

反応ノート

読み込み中…