1H-Isoindole-1,3(2H)-dione, 2-(bromomethyl)- → HCID 67179958, compound

HRID 1259837Notes

Reaction equation

[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:11][O:12][C:13](=[O:28])[CH2:14][C:15]1[C:16]([F:27])=[CH:17][CH:18]=[C:19]2[C:24]=1[N:23]=[C:22]([O:25][CH3:26])[CH:21]=[CH:20]2.Br[CH2:30][N:31]1[C:35](=[O:36])[C:34]2=[CH:37][CH:38]=[CH:39][CH:40]=[C:33]2[C:32]1=[O:41]>C1COCC1>[CH3:11][O:12][C:13](=[O:28])[CH:14]([C:15]1[C:16]([F:27])=[CH:17][CH:18]=[C:19]2[C:24]=1[N:23]=[C:22]([O:25][CH3:26])[CH:21]=[CH:20]2)[CH2:30][N:31]1[C:35](=[O:36])[C:34]2[C:33](=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:32]1=[O:41]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of LiHMDS (1M in THF, 9.6 mL) was added at −78° C. a solution of (7-fluoro-2-methoxy-quinolin-8-yl)-acetic acid methyl ester (2.0 g, 8.0 mmol; prepared as in WO 2007/081597) in THF (16 mL) over 10 min. After stirring the resulting orange mixture for 1 h at −78° C., a solution of N-(bromomethyl)phthalimide (1.2 eq.) in THF (16 mL) was added dropwise over 10 min. The mixture was stirred 1 h at −78° C. and then at rt overnight. The yellow solution was quenched with 1N HCl (80 mL) and then extracted with DCM. The combined org layers were washed with water, dried over MgSO4, concentrated and purified by CC (Hept/EA 1:1) to give 1.89 g of a yellow solid which was recrystallized from EA/MeOH/NH4OH (90:10:1) to afford the title intermediate as a colourless solid (924 mg, 28% yield).

Workup

stirringThe mixture was stirred 1 h at −78° C.
customat rt
customovernight
customThe yellow solution was quenched with 1N HCl (80 mL)
extractionextracted with DCM
washThe combined org layers were washed with water
dry with materialdried over MgSO4
concentrationconcentrated
custompurified by CC (Hept/EA 1:1)

Sources & evidence

ORD record: ord-433cac403849423bb0ba8e6e083d63ea
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08466168B2

Reaction notes

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