1H-Isoindole-1,3(2H)-dione, 2-(bromomethyl)- → HCID 67182524, compound

HRID 1259840Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:19])[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:16][CH3:17])[N:14]=2)[N:9]=[CH:8][C:7]=1[F:18])[CH3:2].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Br[CH2:31][N:32]1[C:36](=[O:37])[C:35]2=[CH:38][CH:39]=[CH:40][CH:41]=[C:34]2[C:33]1=[O:42]>C1COCC1>[CH2:1]([O:3][C:4](=[O:19])[CH:5]([C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:16][CH3:17])[N:14]=2)[N:9]=[CH:8][C:7]=1[F:18])[CH2:31][N:32]1[C:36](=[O:37])[C:35]2[C:34](=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:33]1=[O:42])[CH3:2]

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of (3-fluoro-6-methoxy-[1,5]naphthyridin-4-yl)-acetic acid ethyl ester (6.78 g; prepared in analogy to the corresponding methyl ester described in WO 2007/122258) in THF (30 mL) was added dropwise at −78° C. to a solution of LiHMDS (31 mL; 1M in THF) diluted in THF (20 mL). After stirring for 1 h at −78° C. a solution of N-(bromomethyl)phthalimide (7.40 g) in THF (30 mL) was added dropwise and the mixture was stirred for an additional 1 h at −78° C. and then overnight at rt. The yellow solution was quenched with 1N HCl (280 mL) and extracted with DCM. The combined org. layers were washed with H2O, dried over MgSO4, concentrated and purified by CC (Hept/EA 1:1), affording a light yellow foam (5.49 g; 51% yield).

Workup

additionwas added dropwise
customovernight
customat rt
customThe yellow solution was quenched with 1N HCl (280 mL)
extractionextracted with DCM
washlayers were washed with H2O
dry with materialdried over MgSO4
concentrationconcentrated
custompurified by CC (Hept/EA 1:1)
customaffording a light yellow foam (5.49 g; 51% yield)

Sources & evidence

ORD record: ord-63b2be297e8f4d13ac51dcee0e22fdd7
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08466168B2

Reaction notes

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