N-methyl-2-pyrrolidone → HCID 57552550, compound

HRID 1513860Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH3:19])[CH:14]=3)[C:9]=2[OH:20])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].F[C:24]1[CH:31]=[CH:30][C:27](C=O)=[CH:26][CH:25]=1.CN1CCCC1=[O:38]>>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH3:19])[CH:14]=3)[C:9]=2[O:20][C:24]2[CH:31]=[CH:30][C:27]([OH:38])=[CH:26][CH:25]=2)[CH:5]=[CH:6][CH:7]=1

Participants

Reactant 4

HCID 13387N-methyl-2-pyrrolidone2×

HCID 24758Sodium hydride

HCID 680234-Fluorobenzaldehyde

HCID 670043012-(3-Fluoro-phenyl)-6-methoxy-naphthalen-1-ol

Product 1

HCID 57552550HCID 57552550, compoundYield 54%

Conditions

Temperature: 185 °C

Procedure

Dissolve 2-(3-fluoro-phenyl)-6-methoxy-naphthalen-1-ol (3.36 g, 12.5 mmol) in N-methyl-2-pyrrolidinone (NMP) (10 mL) and add sodium hydride (500 mg, 60% oil dispersion, 12.5 mmol) at room temperature. After stirring for 1 hour this solution is added to a solution of 4-fluorobenzaldehyde (2.4 mL, 22.5 mmol) in NMP (10 mL) that has been heated to 185° C. Continue stirring for 2.5 hours. Cool the reaction to room temperature and add pH 7 buffer (50 mL) and extract with ethyl acetate (2×100 mL). Wash the organic extracts with water and filter through a plug of silica gel. Purify the crude product using radial chromatography giving 2.50 g (54%) of the title compound and use without further purification: mass spectrum (ion spray) m/z=371 (M−H).

Workup

stirringContinue stirring for 2.5 hours
temperatureCool
customthe reaction to room temperature
additionadd pH 7 buffer (50 mL)
extractionextract with ethyl acetate (2×100 mL)
washWash the organic extracts with water
filtrationfilter through a plug of silica gel
customPurify the crude product

Sources & evidence

ORD record: ord-5a1a83ff333a4acf8f712fa67b64e99d
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08217032B2

Reaction notes

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