Water → HCID 10518227, compound

HRID 481342Notes

Reaction equation

HRID 481342 reaction equation
[CH2:1]([N:8]([CH3:30])[C:9](=O)[C:10]([C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([Cl:21])[CH:19]=2)[N:14](C2C=CC(F)=CC=2)[CH:13]=1)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>O1CCCC1>[CH2:1]([N:8]([CH2:9][CH2:10][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([Cl:21])[CH:19]=2)[NH:14][CH:13]=1)[CH3:30])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 19065932HCID 19065932, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 10518227HCID 10518227, compoundYield 92.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 5-chloroindole (20 g, 0.13 mol) in dry diethyl ether (200 mL) was added a solution of oxalylchloride (20 g, 0.16 mol) in dry diehtyl ether (200 mL) at 0°-5° C. After stirring for 0.5 h at 0°-5° C. was added a solution of benzylmethylamine (24 g, 0.20 mol) in dry diethyl ether at 0°-5° C. and triethylamine was slowly added to pH at 8-9. Water and ethyl acetate (500 mL) was added and the organic phase was washed with brine and dried (Na2SO4). Evaporation of the solvents afforded the crude N-benzyl-N-methyl-2-(5-chloro-1-(4-fluorophenyl)-3-1H-indolyl)-2-oxoacetamide (19.1 g) as an oil. A solution of the crude N-benzyl-N-methyl-2-(5-chloro-1-(4-fluorophenyl)-3-1H-indolyl)-2-oxoacetamide (20.1 g, 0.058 mol) in dry tetrahydrofuran (200 mL) was added to a suspension of lithium aluminium hydride (5.4 g, 0.14 mol) in tetrahydrofuran (100 mL). After heating at reflux for 2.5 h the reaction mixture was cooled to 0° C. and treated with water (6 mL) and 4N aqueous NaOH (6 mL). The precipitate was filtered off and extracted with dichloromethane (3×200 mL). The combined organic phases were dried (Na2SO4) and the solvents were evaporated. The remaining oil was purified by column chromatography (eluted with ethyl acetate) affording N-benzyl-N-methyl-2-(5-chloro-3-1H-indolyl)ethylamine (16 g) as an oil: 1H NMR (CDCl3) δ 2.30 (s, 3 H), 2.65-2.80 (m, 2 H), 2.85-3.00 (m, 2 H), 3.60 (s, 2 H), 6.95 (broad s, 1 H), 7.05-7.20 (m, 2 H), 7.15-7.35 (m, 5), 7.45 (broad s,1 H), 8.35 (broad s,1 H).

Workup

  1. temperatureAfter heating
  2. temperatureat reflux for 2.5 h the reaction mixture
  3. filtrationThe precipitate was filtered off
  4. extractionextracted with dichloromethane (3×200 mL)
  5. dry with materialThe combined organic phases were dried (Na2SO4)
  6. customthe solvents were evaporated
  7. customThe remaining oil was purified by column chromatography (eluted with ethyl acetate)

Sources & evidence

ORD record
ord-3430bdc8daee40a58aff73a33879fc56
Source dataset
uspto-grants-1998_08
Patent number
US05789404

Reaction notes

Loading…