Diisopropylamine → 6-Methoxy-2-quinolinepropanoic Acid 1,1-Dimethylethyl Ester

HRID 1648107Notes

Reaction equation

C(NC(C)C)(C)C.C([Li])CCC.C([N-]C(C)C)(C)C.[Li+].[C:21]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])(=[O:23])[CH3:22].Br[CH2:30][C:31]1[CH:40]=[CH:39][C:38]2[C:33](=[CH:34][CH:35]=[C:36]([O:41][CH3:42])[CH:37]=2)[N:32]=1>O1CCCC1.CCOCC>[CH3:26][C:25]([O:24][C:21](=[O:23])[CH2:22][CH2:30][C:31]1[CH:40]=[CH:39][C:38]2[C:33](=[CH:34][CH:35]=[C:36]([O:41][CH3:42])[CH:37]=2)[N:32]=1)([CH3:28])[CH3:27]

Participants

Conditions

Temperature: 10 °C

Procedure

To a solution of diisopropylamine (7.4 mL, 52.8 mmol) in 70 mL of tetrahydrofuran cooled to -78° C. was added a solution of 1.6M n-butyllithium in hexanes (31.4 mL, 50.2 mmol). After being stirred for 12 minutes, the resulting solution of lithium diisopropylamide was treated with a solution of t-butyl acetate (4.81 g, 41.4 mmol) in 70 mL of tetrahydrofuran, added slowly through an addition funnel. The reaction mixture was allowed to warm gradually to 10° C. over 3.75 hr, and then recooled to -78° C. whereupon a solution of 2-(bromomethyl)-6-methoxyquinoline from the preceding example (3.46 g, 13.7 mmol) in 40 mL of tetrahydrofuran was added and the reaction was allowed to stir overnight at room temperature. The resulting solution was worked-up with ether in the usual manner. Flash chromatography of the crude product on 360 g of silica gel, eluting with hexane-ethyl acetate (4:1) afforded 1.31 g (33.8 %) of the title compound as an orange oil.

Workup

additionadded slowly through an addition funnel
additionwas added
stirringto stir overnight at room temperature
washFlash chromatography of the crude product on 360 g of silica gel, eluting with hexane-ethyl acetate (4:1)

Sources & evidence

ORD record: ord-c53c32b8376b46649aa5590da62458e8
Source dataset: uspto-grants-1995_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05434186

Reaction notes

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