Hexamethylphosphoramide → 1-(2,3-Dichlorobenzoyl)-5-methoxy-2-methyl-(3-(morpholin-4-yl)ethyl)-1H-indole hydrochloride

HRID 1733857Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([CH3:12])=[C:6]2[CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1.CN(P(N(C)C)(N(C)C)=O)C.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[Cl:42][C:43]1[C:51]([Cl:52])=[CH:50][CH:49]=[CH:48][C:44]=1[C:45](Cl)=[O:46]>C1COCC1.C([O-])(O)=O.[Na+]>[Cl:42][C:43]1[C:51]([Cl:52])=[CH:50][CH:49]=[CH:48][C:44]=1[C:45]([N:8]1[C:9]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:11][CH:10]=2)[C:6]([CH2:13][CH2:14][N:15]2[CH2:16][CH2:17][O:18][CH2:19][CH2:20]2)=[C:7]1[CH3:12])=[O:46]

Participants

Conditions

Temperature: -22 °C

Procedure

To 5-methoxy-2-methyl-3-(2-(morpholin-4-yl)ethyl)- 1H-indole (311 mg; 1.13 mmol) in 10 mL dry THF at -78° C. was added HMPA (590 μL; 3.39 mmol), then dropwise KHMDS (0.5M in Tol; 2.5 mL; 1.25 mmol). The solution was stirred 30 min at -22° C. then cooled to -78° C. after which 2,3-dichlorobenzoyl chloride (361 mg; 1.72 mmol) was added. The final mixture was allowed to reach r.t. slowly then stirred 1 h. The mixture was poored in saturated NaHCO3 (25 mL), extracted with EtOAc (2×50 mL). The organic phase was washed with brine (50 mL), dried over Na2SO4, filtered, concentrated and flash chromatographed (Silica gel; EtOAc) to yield 503 mg (99%) of the title compound.

Workup

additionwas added
customto reach r.t.
stirringstirred 1 h
extractionextracted with EtOAc (2×50 mL)
washThe organic phase was washed with brine (50 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customflash chromatographed (Silica gel; EtOAc)

Sources & evidence

ORD record: ord-4560ed8d626c46dc95d8cd640d058390
Source dataset: uspto-grants-1996_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05532237

Reaction notes

Loading…