Sodium Hydroxide → HCID 21868747, compound

HRID 392078Notes

Reaction equation

HRID 392078 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][C:8]1[CH:16]=[C:15]2[C:11]([CH:12]=[C:13]([C:20]([O:22]C)=[O:21])[N:14]2[CH2:17][C:18]#[N:19])=[CH:10][CH:9]=1.[OH-:24].[Na+].S([O-])([O-])(=O)=[O:27].[Mg+2]>CCOCC.O>[C:20]([OH:22])(=[O:21])/[CH:13]=[CH:12]/[C:11]([OH:27])=[O:24].[Cl:7][C:8]1[CH:9]=[CH:10][C:11]2[CH:12]=[C:13]3[CH2:20][NH:19][CH2:18][CH2:17][N:14]3[C:15]=2[CH:16]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24083Sulfuric acid magnesium salt (1:1)HCID 21226445Aluminium lithium hydrideHCID 21868736HCID 21868736, compound

Product 1

HCID 21868747HCID 21868747, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 3283Diethyl EtherSolvent

Procedure

To a stirred suspension of lithium aluminium hydride (95%; 1.18 g, 29.5 mmol) in anhydrous ether (150 mL) under Ar at 14° C. was added portionwise, over 20 min, methyl 6-chloro-1-(cyanomethyl)-indole-2-carboxylate (2.95 g, 11.9 mmol), allowing the internal temperature to stay at, or below 25° C. After addition was complete, the mixture was heated at reflux for 18 h, then allowed to cool. Water (1.18 mL) was cautiously added, followed by 15% aqueous sodium hydroxide (1.18 mL), then water (3.5 mL). After stirring for 30 min, magnesium sulfate was added and the mixture was filtered through Kieselguhr and washed through with ether (50 mL). The solvent was removed in vacuo and the residue was purified by flash chromatography [SiO2; ethyl acetate-methanol (9:1)] to afford the free-base of the title compound (1.38 g, 56%) as a pale yellow solid: NMR δH (400 MHz, CDCl13) 1.64 (1H, br s), 3.35 (2H, t, J 5.5 Hz), 3.96 (2H, t, J 5.5 Hz), 4.19 (2H, d, J 1.0 Hz), 6.16 (1H, d, J 1.0 Hz). 7.04-7.08 (1H, m), 7.23-7.26 (1H, m), and 7.43 (1H, d, J 8.5 Hz). To a sample of the free-base (130 mg, 0.63 mmol) in 2-propanol (4 mL) was added fumaric acid (110 mg, 0.95 mmol) and the mixture was heated to reflux for 1 min. The resultant suspension was allowed to cool to ambient temperature, and then cooled in ice. The solid was filtered and washed with ice-cold 2-propanol (3 mL) to afford the title compound (184 mg, 90%) as a pale yellow solid: mp 202.5° C. (dec.); NMR δH (400 MHz, DMSO-d6) 3.26 (2H, t, J 5.5 Hz), 4.01 (2H t, J 5.5), 4.12 (2H, s), 7.01 (1H, dd, J 8.0, 2.0 Hz) and 7.45-7.49 (2H, m); Found: C, 55.90; H, 4.72; N, 8.58%. C15H15ClN2O4 requires C, 55.82; H. 4.68; N, 8.68%.

Workup

  1. additionwas added portionwise, over 20 min
  2. custombelow 25° C
  3. additionAfter addition
  4. temperaturethe mixture was heated
  5. temperatureat reflux for 18 h
  6. temperatureto cool
  7. filtrationthe mixture was filtered through Kieselguhr
  8. washwashed through with ether (50 mL)
  9. customThe solvent was removed in vacuo
  10. customthe residue was purified by flash chromatography [SiO2; ethyl acetate-methanol (9:1)]

Sources & evidence

ORD record
ord-c71e697d900e47ef8192ae682703c7e1
Source dataset
uspto-grants-2004_10
Patent number
US06800627B1

Reaction notes

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