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

HRID 2061143Notes

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-0671f1612ea54dcf91d2a4f6416a9c46
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278465B2

Reaction notes

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