Hydrochloric Acid → [3-(tert-Butoxycarbonyl)-9,10-dichloro-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl]acetic acid

HRID 1370424Notes

Reaction equation

[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][C:12]([O:14]CC)=[O:13])[C:6]3[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:20][CH2:21][C:5]=3[C:4]=2[C:3]=1[Cl:29].[OH-].[K+].Cl>C1COCC1.O>[C:25]([O:24][C:22]([N:19]1[CH2:20][CH2:21][C:5]2[C:4]3[C:3]([Cl:29])=[C:2]([Cl:1])[CH:10]=[CH:9][C:8]=3[N:7]([CH2:11][C:12]([OH:14])=[O:13])[C:6]=2[CH2:17][CH2:18]1)=[O:23])([CH3:28])([CH3:26])[CH3:27]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of tert-butyl 9,10-dichloro-6-(2-ethoxy-2-oxoethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (1.5 g, 3.4 mmol) in THF (15 mL), a solution of KOH (25 mg, 4.4 mmol) dissolved in H2O (10 mL) was added and heated to 60° C. The reaction was cooled to rt after 2 h. The reaction was made acidic with 10% aqueous HCl and extracted with EtOAc (3×30 mL). The combined organic extracts were washed with brine, dried over Na2SO4, decanted, and the crude acid was concentrated: 1H NMR (300 MHz, DMSO) δ 13.11 (br s, 1H), 7.43 (d, J=8.8 Hz, 1H), 7.23 (d, J=8.7 Hz, 1H), 5.04 (s, 2H), 3.62 (m, 4H), 2.93 (m, 2H), 1.41 (s, 9H); HRMS (FAB) calcd for C19H22Cl2N2O4+H 413.1035, found 413.1050.

Workup

additionwas added
temperatureThe reaction was cooled to rt after 2 h
extractionextracted with EtOAc (3×30 mL)
washThe combined organic extracts were washed with brine
dry with materialdried over Na2SO4
customdecanted
concentrationthe crude acid was concentrated

Sources & evidence

ORD record: ord-7a1f2374291447d7adb5468222ce91d7
Source dataset: uspto-grants-2003_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06583135B2

Reaction notes

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