Hydrochloric Acid → Lidorestat

HRID 1581774Notes

Reaction equation

HRID 1581774 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

HCID 157839LidorestatYield 98%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

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) δ7.74-7.65 (m, 1H), 7.53 (d, J=7.5 Hz, 1H), 7.46 (s, 1H), 7.40 (d, J=8.1 Hz, 1H), 7.15 (b t, J=6.9 Hz, 1H), 7.03 (b t, J=7.2 Hz, 1H), 5.03 (s, 2H), 4.65 (s, 2H); 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.

Workup

  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

Sources & evidence

ORD record
ord-136da8fa6a644c3299ae3b6fd707a23b
Source dataset
uspto-grants-2004_05
Patent number
US06730794B2

Reaction notes

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