Hydrochloric Acid → Lidorestat

HRID 323839ノート

反応式

HRID 323839 の反応式
[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]

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 9844135HCID 9844135、化合物

生成物 1

HCID 157839Lidorestat収率 98%

試薬・触媒・溶媒 1

HCID 80711,2-Dimethoxyethane溶媒

実験手順

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 suspension 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 C16H11F3N2O2S: 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.

後処理

  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 suspension in heptane
  10. filtrationfiltered
  11. customdried

出典と根拠

ORDレコード
ord-98574119433b4f68beba25709da28bbc
出典データセット
uspto-grants-2001_04
特許番号
US06214991B1

反応ノート

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