Sodium Chloride → HCID 178490111, compound

HRID 1869414Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:18])[CH2:9][C:10]([OH:17])([C:13]([F:16])([F:15])[F:14])[CH:11]=O)=[CH:4][C:3]=1[O:19][CH3:20].[NH2:21][C:22]1[CH:31]=[CH:30][C:29]([F:32])=[C:28]2[C:23]=1[CH:24]=[N:25][C:26]([CH3:33])=[N:27]2.[Cl-].[Na+].[CH3:36]C1C=CC=CC=1C>[Ti+4]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:18])([CH3:36])[CH2:9][C:10](/[CH:11]=[N:21]/[C:22]2[CH:31]=[CH:30][C:29]([F:32])=[C:28]3[C:23]=2[CH:24]=[N:25][C:26]([CH3:33])=[N:27]3)([OH:17])[C:13]([F:14])([F:15])[F:16])=[CH:4][C:3]=1[O:19][CH3:20]

Participants

Conditions

Temperature: 120 °C

Procedure

350 mg (1.08 mmol) of (rac.)-4-(4-chloro-3-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)-pentanal is mixed in 5.8 ml of o-xylene with 190.9 mg (1.08 mmol) of 5-amino-8-fluoro-2-methylquinazoline. After 0.64 ml (2.16) titanium(IV) isopropylate is added, it is refluxed for three hours (bath temperature 120° C.). After cooling, the batch is added to saturated sodium chloride solution and stirred vigorously for 20 minutes. After 2× extraction with ethyl acetate, the combined organic extracts are washed with brine. After drying on sodium sulfate, and after the desiccant is suctioned off and the solvent is spun off, the residue is chromatographed on silica gel (mobile solvent ethyl acetate/hexane). 327.5 mg (62.8%) of the desired imine is isolated.

Workup

temperatureAfter cooling
extractionAfter 2× extraction with ethyl acetate
washthe combined organic extracts are washed with brine
customAfter drying on sodium sulfate
customthe residue is chromatographed on silica gel (mobile solvent ethyl acetate/hexane)

Sources & evidence

ORD record: ord-33cbdcd0d51b4e1d98a08da511f4c502
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07638515B2

Reaction notes

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