Benzoic Acid → methyl N-((6-chloro-4-hydroxy-2-oxo-1'-(phenylcarbonyl)-spiro[naphthalene-1,4'-piperidin]-3-yl)carbonyl)glycinate

HRID 2078278Notes

Reaction equation

HRID 2078278 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[C:8]1([CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[C:7](=[O:17])[C:6]([C:18]([NH:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[O:19])=[C:5]2[OH:26].CCN(C(C)C)C(C)C.[C:36](O)(=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.CS(C)=O.CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[C:8]1([CH2:9][CH2:10][N:11]([C:36]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[O:43])[CH2:12][CH2:13]1)[C:7](=[O:17])[C:6]([C:18]([NH:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[O:19])=[C:5]2[OH:26]

Participants

8

Reactant 4

HCID 243Benzoic AcidHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67099723Methyl N-((6-chloro-4-hydroxy-2-oxo-spiro[naphthalene-1,4'-piperidin]-3-yl)carbonyl)glycinate

Product 1

HCID 67100267methyl N-((6-chloro-4-hydroxy-2-oxo-1'-(phenylcarbonyl)-spiro[naphthalene-1,4'-piperidin]-3-yl)carbonyl)glycinate

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 3013483N,N-dimethylformamide; methylsulfinylmethaneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of the hydrochloride salt of methyl N-((6-chloro-4-hydroxy-2-oxo-spiro[naphthalene-1,4′-piperidin]-3-yl)carbonyl)glycinate (0.050 g, 0.12 mmol) and Hunig's base (0.024 mL, 0.14 mmol) in DMF/DMSO (2:1, 1.5 mL) was stirred at 25° C. for 5 minutes. A mixture of benzoic acid (0.067 g, 0.54 mmol) and N-(3-dimethylaminopropyl)-n′-ethylcarbodiimide hydrochloride (0.13 g, 0.65 mmol) in DMF (1 mL) was added. The mixture was stirred at 60° C. for 8 hours. The solution was diluted with EtOAc (20 mL), and washed with brine (2×25 mL). The organic layer was dried over MgSO4, concentrated, and purified by flash column chromatography (silica, 0-1% MeOH in DCM) to give methyl N-((6-chloro-4-hydroxy-2-oxo-1′-(phenylcarbonyl)-spiro[naphthalene-1,4′-piperidin]-3-yl)carbonyl)glycinate. MS m/e=483.5 (M+H)+.

Workup

  1. additionwas added
  2. washwashed with brine (2×25 mL)
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (silica, 0-1% MeOH in DCM)

Sources & evidence

ORD record
ord-4452c07de4b64972820e5ac99335d462
Source dataset
uspto-grants-2011_04
Patent number
US07928139B2

Reaction notes

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