Water → (R)-5-Bromo-3-(1-methyl-2-pyrrolidinyl methyl)-1H-indole

HRID 1970087Notes

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[C:11]([C@H:13]1[CH2:17][CH2:16][CH2:15][N:14]1[C:18](OCC1C=CC=CC=1)=O)=O.[H-].[H-].[H-].[H-].[Li+].[Al+3].O.[OH-].[Na+]>C1COCC1>[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:13]1[CH2:17][CH2:16][CH2:15][N:14]1[CH3:18]

Participants

Conditions

Temperature: 22.5 °C

Procedure

A solution composed of 205 g of benzyl (2R)-2-[(5-bromo-1H-indole-3-yl)carbonyl]pyrrolidine-1-carboxylate in 820 mL of THF was dropped at 60° C. in 30 minutes into a flask containing 307.5 mL of THF and 479.2 mL of 10% LiAlH4. After 3 hours of reflux the control HPLC showed completion of the reaction and the reaction mixture was cooled to 20-25° C. At this temperature a mixture composed of 20.5 mL of H2O and 82 mL of THF was dropped in 15 minutes approximately. Then other 20.5 mL of H2O were added in about 15 minutes, then 41 ml, of 15% NaOH in about 15 minutes, and lastly other 123 mL of H2O in 15 minutes. After stirring for 30 minutes the salts were filtered, washing the cake with 410 mL of isopropanol. The reaction mixture (HPLC assay 65.3%) was concentrated to residue, obtaining 165.3 g of oil. This residue was diluted with 410 mL of isopropanol and used to obtain the oxalate salt.

Workup

additionwas dropped at 60° C. in 30 minutes into a flask
temperatureAfter 3 hours of reflux the control HPLC
customcompletion of the reaction
additionwas dropped in 15 minutes approximately
filtrationwere filtered
washwashing the cake with 410 mL of isopropanol
concentrationThe reaction mixture (HPLC assay 65.3%) was concentrated to residue

Sources & evidence

ORD record: ord-a518157bf9354a44ae138a0418a1f24d
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08426612B2

Reaction notes

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