Sodium Hydroxide → HCID 59404402, compound

HRID 1873666Notes

Reaction equation

[Cl:1][CH2:2][C:3](N(C)C)=[O:4].O=P(Cl)(Cl)Cl.[CH:13]1[C:23]2=[C:24]3[C:19](=[CH:20][CH:21]=[CH:22]2)[CH2:18][CH2:17][CH2:16][N:15]3[CH:14]=1.[OH-].[Na+]>C(Cl)Cl>[Cl:1][CH2:2][C:3]([C:13]1[C:23]2=[C:24]3[C:19](=[CH:20][CH:21]=[CH:22]2)[CH2:18][CH2:17][CH2:16][N:15]3[CH:14]=1)=[O:4]

Participants

Conditions

Temperature: 80 °C

Procedure

To an ice-cooled solution of 2-chloro-N,N-dimethyl-acetamide (10 mL, 97.5 mmol) was added POCl3 (14 mL, 149.5 mmol). The clear mixture was stirred at room temperature for 20 min 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline (10.20 g, 65.0 mmol, for preparation see WO06086486A1) was added. The mixture was stirred at 80° C. for two hours. The mixture was poured on to ice (200 mL) and dichloromethane (300 mL). Aqueous sodium hydroxide was added to adjust to pH>12. The dichloromethane layer was separated, washed with water (300 mL), dried over Na2SO4, filtered and evaporated to give a dark solid. The solid was dissolved into DCM and purified by silica gel column chromatography (eluent: 0% to 1% EtOAc in DCM). 2-Chloro-1-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-ethanone was obtained as an off-white solid (10.82 g, 71%) after tituration with EtOAc. M.p.=118-119° C.; 1H NMR (400 MHz, CDCl3) δ: 8.00 (d, J=8.0 Hz, 1H), 7.82 (s, 1H), 7.23 (m, 1H), 7.03 (d, J=7.2 Hz, 1H), 4.51 (s, 2H), 4.21 (t, J=6.0 Hz, 2H), 3.01 (t, J=6.0 Hz, 2H), 2.27 (m, 2H). LCMS: m/e 234.03 [M+H].

Workup

additionwas added
customThe dichloromethane layer was separated
washwashed with water (300 mL)
dry with materialdried over Na2SO4
filtrationfiltered
customevaporated
customto give a dark solid
custompurified by silica gel column chromatography (eluent: 0% to 1% EtOAc in DCM)

Sources & evidence

ORD record: ord-d60a59c5f40e4034a8a691d8946b66a3
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08304425B2

Reaction notes

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