Sodium Hydroxide → HCID 44514740, compound

HRID 1970089Notes

Reaction equation

HRID 1970089 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[CH3:17].[C:18]([OH:25])(=[O:24])/[CH:19]=[CH:20]/[C:21]([OH:23])=[O:22].C([O-])(=O)/C=C/C([O-])=O.[OH-].[Na+]>O.C(O)(C)C>[C:18]([OH:25])(=[O:24])/[CH:19]=[CH:20]/[C:21]([OH:23])=[O:22].[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[CH3:17]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 444972Fumaric Acid2×HCID 5460307FumarateHCID 11185464(R)-5-Bromo-3-(1-methyl-2-pyrrolidinyl methyl)-1H-indole

Product 1

HCID 44514740HCID 44514740, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent2×

Conditions

Temperature
22.5 °C

Procedure

A solution of 10 g of 5-bromo-3-{[(2R)-1-methylpyrrolidin-2-yl]methyl}-1H-indole (as oil containing traces of toluene, HPLC purity 98.3%) in 20 ml, of isopropanol, were dropped in about 2 hours at 30-35° C. into a solution composed of 65 ml, of isopropanol, 15 mL of water and 4.4 g of anhydrous fumaric acid. After stirring for 2 hours at 20-25° C. the reaction mixture was filtered and the crystalline product dried at 80° C. obtaining 7.12 g (Karl Fischer 0.08%, HPLC purity 99.4%). By cooling the mother liquors at −15° C., 1.23 g (Karl Fischer 0.17%, HPLC purity 99.0%) were further obtained. The product (molecule 7 fumarate) has a 199.4° C. (DSC 10°/min) melting point, 1H-NMR (DMSO-d6) spectrum: δ 11.18 (br s, 1H), 7.75 (d, j=1.9 Hz, 1H), 7.3 (d, j=8.6 Hz, 1H) 7.3 (d, j=2.3 Hz, 1H), 7.18 (dd, j=1.9 Hz and 8.6 Hz, 1H), 6.54 (s, 2H), 3.41-3.31 (m, 1H), 3.21 (dd, j=14 Hz and 4.5 Hz, 1H), 3.13-3.02 (m, 1H), 2.8-2.65 (m, 2H), 2.62 (s, 3H), 1.92-1.72 (m, 3H), 1.70-1.56 (m, 1H) and a titre with NaOH corresponding to a 1:1 stoichiometry with fumaric acid.

Workup

  1. filtrationwas filtered
  2. customthe crystalline product dried at 80° C.
  3. customobtaining 7.12 g (Karl Fischer 0.08%, HPLC purity 99.4%)
  4. temperatureBy cooling the mother liquors at −15° C.
  5. custom1.23 g (Karl Fischer 0.17%, HPLC purity 99.0%) were further obtained
  6. customhas a 199.4° C.

Sources & evidence

ORD record
ord-7812bad1d9c649528c421a2f8d2c4d53
Source dataset
uspto-grants-2013_04
Patent number
US08426612B2

Reaction notes

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