Hydrochloric Acid → Lidorestat

HRID 2212819노트

반응식

HRID 2212819 반응식
[F:1][C:2]1[C:7]2[N:8]=[C:9]([CH2:11][C:12]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]([CH2:21][C:22]([O:24]CC)=[O:23])[CH:13]=3)[S:10][C:6]=2[C:5]([F:27])=[CH:4][C:3]=1[F:28].[OH-].[Na+].Cl>COCCOC>[F:1][C:2]1[C:7]2[N:8]=[C:9]([CH2:11][C:12]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]([CH2:21][C:22]([OH:24])=[O:23])[CH:13]=3)[S:10][C:6]=2[C:5]([F:27])=[CH:4][C:3]=1[F:28]

참가 물질

5

반응물 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 9844135HCID 9844135, 화합물

생성물 1

HCID 157839Lidorestat수율 98%

시약·촉매·용매 1

HCID 80711,2-Dimethoxyethane용매

실험 절차

A solution of give 3-(4,5,7-trifluorobenzothiazol-2-yl)methyl-indole-N-acetic acid, ethyl ester (5.91 g, 14.6 mmol) in 1,2-dimethoxyethane (73 mL, 0.2 M) was cooled to 0° C. and treated with aq. NaOH (1.25 N, 58 mL, 73.1 mmol) in a dropwise manner over 15 min. After the addition was complete, the solution was stirred for an additional 30 min, acidified to pH 3 with 2N HCl, and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (200 mL) and washed with sat'd. aq. NaCl (30 mL). The organic extract was dried over Na2SO4, filtered and concentrated. The resulting material was stirred as a supension in heptane, filtered and dried to give 3-(4,5,7-trifluorobenzothiazol-2-yl)methyl-indole-N-acetic acid (5.38 g, 98%) as a pale yellow solid: mp 177-178° C.; Rf 0.44 (20% methanol in dichloromethane); 1H NMR (DMSO-d6, 300 MHz) δ 7.74-7.65 (m, 1 H), 7.53 (d, J=7.5 Hz, 1 H), 7.46 (s, 1 H), 7.40 (d, J=8.1 Hz, 1 H), 7.15 (b t, J=6.9 Hz, 1 H), 7.03 (b t, J=7.2 Hz, 1 H), 5.03 (s, 2 H), 4.65 (s, 2 H); LRMS calcd for C18H11F3N2O2S: 376.4. found 375.0 (M−1)−. Anal. Calcd for C18H11F3N2O2S: C, 57.44; H, 2.95; N, 7.44; S, 8.52. Found C, 57.58; H, 2.99; N, 7.38; S, 8.51.

후처리

  1. additionAfter the addition
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate (200 mL)
  4. washwashed with sat'd
  5. extractionThe organic extract
  6. dry with materialwas dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. stirringThe resulting material was stirred as a supension in heptane
  10. filtrationfiltered
  11. customdried

출처 및 근거

ORD 기록
ord-8f4677286e324b98bb0bccc7bb999dff
출처 데이터셋
uspto-grants-2006_09
특허 번호
US07105514B2

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