Hydrochloric Acid → Methyl 3-(2-fluorophenyl)-2-(2-(isopropylamino)benzo[d]thiazol-6-yl)-3-oxopropanoate

HRID 1452961Notes

Reaction equation

C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH:11]([NH:14][C:15]1[S:16][C:17]2[CH:23]=[C:22]([CH2:24][C:25]([O:27][CH3:28])=[O:26])[CH:21]=[CH:20][C:18]=2[N:19]=1)([CH3:13])[CH3:12].[F:29][C:30]1[CH:39]=[CH:38][CH:37]=[CH:36][C:31]=1[C:32](OC)=[O:33].Cl>C1COCC1>[F:29][C:30]1[CH:39]=[CH:38][CH:37]=[CH:36][C:31]=1[C:32](=[O:33])[CH:24]([C:22]1[CH:21]=[CH:20][C:18]2[N:19]=[C:15]([NH:14][CH:11]([CH3:12])[CH3:13])[S:16][C:17]=2[CH:23]=1)[C:25]([O:27][CH3:28])=[O:26]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of lithium bis(trimethylsilyl)amide (1.0 M in THF, 15.1 mL) in THF (30 mL) was added a solution of methyl 2-(2-(isopropylamino)benzo[d]thiazol-6-yl)acetate (1.60 g, 6.05 mmol) in THF (20 mL) at −78° C. over 40 min. The resulting solution was stirred at −78° C. for 15 min before a solution of methyl 2-fluorobenzoate (1.08 mL, 8.48 mmol) in THF (10 mL) was added over 5 min. The mixture was stirred at −78° C. for 1 hr and then at rt for 3 hr before it was poured into ice-cold water (100 mL). After its pH value was adjusted to 9 with 6 N HCl, the mixture was extracted with AcOEt (3×40 mL). The combined extract was washed with brine and dried over anhydrous MgSO4. Evaporation of solvent under vacuum give the title compound (2.81 g) as an orange yellowish oil. This product was 63% pure by LCMS, but it was used in the next step without further purification.

Workup

additionwas added over 5 min
extractionthe mixture was extracted with AcOEt (3×40 mL)
extractionThe combined extract
washwas washed with brine
dry with materialdried over anhydrous MgSO4
customEvaporation of solvent under vacuum

Sources & evidence

ORD record: ord-0504142bb8c3456b989752ae022de051
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07473784B2

Reaction notes

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