Lithium Hydroxide → 2-[2-(Benzhydrylidene-amino)-3-fluoropyridin-4-ylmethyl]-3-oxobutanoic acid ethyl ester

HRID 599860Notes

Reaction equation

[C:1](=[N:14][C:15]1[C:20]([F:21])=[C:19]([CH2:22]O)[CH:18]=[CH:17][N:16]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(Cl)(=O)=O.CC(C)([O-])C.[Li+].[CH2:35]([O:37][C:38](=[O:43])[CH2:39][C:40]([CH3:42])=[O:41])[CH3:36].[Na+].[I-].[Li+].[OH-]>C1COCC1.C(OCC)(=O)C>[CH2:35]([O:37][C:38](=[O:43])[CH:39]([CH2:22][C:19]1[CH:18]=[CH:17][N:16]=[C:15]([N:14]=[C:1]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:20]=1[F:21])[C:40](=[O:41])[CH3:42])[CH3:36]

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of [2-(benzhydrylidene-amino)-3-fluoropyridin-4-yl]-methanol (compound 8c-4) (5 g, 16.3 mmol), methanesulfonyl chloride (1.52 mL, 19.6 mmol) and lithium tert-butoxide (in THF) (18 mL, 18 mmol) in THF (40 mL) was stirred at 0° C. for 1 hour. The mixture was added to a solution of acetoacetic acid ethyl ester (4.16 mL, 32.7 mmol), lithium tert-butoxide (in THF) (19.6 mL, 19.6 mmol) and NaI (2.5 g, 16.3 mmol) in THF (18 mL). The solution was stirred at 50° C. for 3 hours, 0.2N LiOH (in water) and ethyl acetate were added thereto, and the solution was washed with 0.2N LiOH (in water) and saturated saline. After drying over anhydrous magnesium sulfate, the solvent was distilled away under reduced pressure to yield the title compound (6.98 g, quant.).

Workup

stirringThe solution was stirred at 50° C. for 3 hours
washthe solution was washed with 0.2N LiOH (in water) and saturated saline
dry with materialAfter drying over anhydrous magnesium sulfate
distillationthe solvent was distilled away under reduced pressure

Sources & evidence

ORD record: ord-6637341028af40e1bd4471cd504d355d
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07897792B2

Reaction notes

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