Hydrochloric Acid → HCID 66669012, compound

HRID 1618054Notes

Reaction equation

HRID 1618054 reaction equation
C[O:2][C:3]1[N:8]=[CH:7][C:6]([C:9](=[O:38])[CH2:10][C@H:11]([C:19]2[CH:24]=[CH:23][C:22]([CH:25]3[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]3)=[CH:21][CH:20]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])=[CH:5][CH:4]=1.[ClH:39]>O>[ClH:39].[NH:28]1[CH2:29][CH2:30][CH:25]([C:22]2[CH:21]=[CH:20][C:19]([C@H:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[CH3:18])[CH2:10][C:9]([C:6]3[CH:5]=[CH:4][C:3](=[O:2])[NH:8][CH:7]=3)=[O:38])=[CH:24][CH:23]=2)[CH2:26][CH2:27]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 66666519HCID 66666519, compound

Product 1

HCID 66669012HCID 66669012, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of (R)-tert-butyl 4-(4-(3-(6-methoxypyridin-3-yl)-3-oxo-1-o-tolylpropyl)-phenyl)piperidine-1-carboxylate (260 mg, 505 μmol), hydrogen chloride solution (4.0 M in 1,4-dioxane, 3.03 mL, 12.1 mmol) and water (0.5 mL) was heated to 100° C., then after 90 min the reaction mixture was purged with argon and concentrated to afford (R)-5-(3-(4-(piperidin-4-yl)phenyl)-3-o-tolylpropanoyl)pyridin-2(1H)-one hydrochloride (272 mg, light yellow foam, MS (ESI+): m/z=: 401.4 [M+H]+). This was taken up in dichloromethane (4 mL) and N,N-dimethylformamide (0.4 mL), then after addition of N,N-diisopropylethylamine (326 mg, 2.53 mmol) and a solution of di-tert-butyl-dicarbonate (121 mg, 0.56 mmol) at 0° C. After 30 min the reaction mixture was partitioned between sat. aq. sodium hydrogencarbonate solution and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated. Chromatography (SiO2; gradient ethyl acetate/heptane 1:1 to ethyl acetate) afforded the title compound (204 mg, 81%). Light yellow foam, MS (ESI+): m/z=: 501.1 [M+H]+.

Workup

  1. customafter 90 min the reaction mixture was purged with argon
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-e454bfe9caaa4fae881c2e1ab3a2eaac
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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