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

HRID 537526노트

반응식

HRID 537526 반응식
[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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 887Methanol용매HCID 962Water용매

반응 조건

온도
35 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-7fe2b339620b4778ac72615870fdce4a
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08859591B2

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