Hydrochloric Acid → HCID 131730405, compound

HRID 1963414Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:13][C@H:12]([C:14](=[O:21])[CH2:15][C:16](OCC)=[O:17])[CH2:11][CH2:10][N:9]2[C:22]([O:24][CH3:25])=[O:23])=[C:4]([F:26])[CH:3]=1.[OH-].[Na+].[NH2:29]O.Cl>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:13][C@H:12]([C:14]3[O:21][NH:29][C:16](=[O:17])[CH:15]=3)[CH2:11][CH2:10][N:9]2[C:22]([O:24][CH3:25])=[O:23])=[C:4]([F:26])[CH:3]=1

Participants

Conditions

Temperature: -40 °C

Procedure

Trans-methyl 2-(4-chloro-2-fluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (500 mg, 1.30 mmol) (from example 45, step 1) was dissolved in MeOH (6 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (0.381 mL, 1.30 mmol) was added during 10 min and the yellow solution continued to stir at −40° C. for 20 min. Hydroxylamine (50% by weight in water, 0.079 mL, 1.30 mmol) was added during 8 min. The resulting solution was stirred at −40° C. for 3 h. The mixture was then rapidly poured into a prewarmed (80° C.) solution of 6 M hydrogen chloride (6.67 mL, 40.05 mmol) and the mixture continued to stir at 80° C. for 20 min. The solvent was evaporated and DCM/water added. The phases were separated and the organic phase passed through a phase separator and evaporated to yield crude trans-methyl 2-(4-chloro-2-fluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.45 g, 98%) as a slightly yellow dry film. MS m/z 355 (M+H)+

Workup

stirringThe resulting solution was stirred at −40° C. for 3 h
stirringto stir at 80° C. for 20 min
customThe solvent was evaporated
additionDCM/water added
customThe phases were separated
customevaporated

Sources & evidence

ORD record: ord-93cafac114f14e85adfb4cd0b4232181
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415378B2

Reaction notes

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