3-Bromopropionic acid → 1,1,2-trimethyl[1H]-benz[e]indole-3-propanoic acid

HRID 555901

Reaction equation

[CH3:1][C:2]1([CH3:47])[C:14](/[CH:15]=C/C=C/C=C/C=C2\C(C)(C)C3C4C=CC=CC=4C=CC=3N\2CCC(O)=O)=[N+:13]([CH2:42][CH2:43][C:44]([OH:46])=[O:45])[C:12]2[CH:11]=[CH:10][C:9]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[C:3]1=2.[Br-].CC1(C)C2C3C=CC=CC=3C=CC=2N=C1C.BrCCC(O)=O>ClC1C=CC=CC=1Cl>[CH3:1][C:2]1([CH3:47])[C:3]2[C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:9]=3[CH:10]=[CH:11][C:12]=2[N:13]([CH2:42][CH2:43][C:44]([OH:46])=[O:45])[CH:14]1[CH3:15]

Participants

Conditions

Temperature: 110 °C

Procedure

To synthesize cypate, a mixture of 1,1,2-trimethyl-[1H]-benz[e]indole (40.0 g, 19.11 mmol) and 3-bromopropanoic acid (40.0 g, 26.15 mmol) in 1,2-dichlorobenzene (200 mL) was heated at 110° C. for 18 h. After the resulting mixture was cooled to room temperature, the precipitate was collected by filtration, followed by trituration in dichloromethane (DCM) to remove the un-reacted material, and then dried under vacuum to afford 1,1,2-trimethyl[1H]-benz[e]indole-3-propanoic acid. A solution of acetic anhydride (1.20 g, 11.75 mmol) in DCM (5 mL) was added dropwise to a cooled suspension of glutaconaldehyde dianil monohydrochloride (2.84 g, 9.97 mmol) and diisopropylethylamine (DIEA, 2.60 g, 20.11 mmol) in DCM (20 mL). The resulting clear solution was stirred for 1 h and added dropwise to a refluxing solution of 1,1,2-trimethyl[1H]-benz[e]indole-3-propanoic acid (8.2 g, 22.64 mmol) and sodium acetate (3.2 g, 39.01 mmol) in acetonitrile/water (95/5 mL). The mixture was refluxed for 16 h, cooled, filtered, and washed with acetonitrile, 5% HCl solution and ethyl ether. About 6 g (85%) of cypate was obtained. It was further purified by recrystallization from 30% acetonitrile in water. Mass calculated: 625; observed (ESI-MS): 625.34 [M]+.

Workup

temperatureAfter the resulting mixture was cooled to room temperature
filtrationthe precipitate was collected by filtration
customto remove the un-reacted material
customdried under vacuum

Sources & evidence

ORD record: ord-4210f45d34934bb0871efdc03ce67d9d
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08053415B2

Linked notes

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