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

HRID 328042Notes

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 additional 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 resuting 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 additional 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-ef38bbd62ddd490d82c23b9062e9af04
Source dataset: uspto-grants-1993_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05273999

Reaction notes

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