반응 #1929069

반응 방정식

triethylamine

compound

Methyl 1-amino-4,4-difluorocyclohexanecarboxylate hydrochloride

triethylamine

phosphorus oxychloride

(4′-chloro-4-methylbiphenyl-3-yl)acetic acid

→

Methyl 1-{[(4′-chloro-4-methylbiphenyl-3-yl)acetyl]amino}-4,4-difluorocyclohexanecarboxylate

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   workup.WAITAfter 15 min
2. 2
   workup.STIRRINGthe mixture was stirred
3. 3
   온도under reflux for 30 min
4. 4
   농축The mixture was concentrated under reduced pressure
5. 5
   기타the residue was purified by means of flash chromatography on silica gel using the mobile phase n-hexane/ethyl acetate 1:1

실험 절차

2.53 g (11 mmol) of the compound from Example 4A were initially charged in 50 ml of absolute tetrahydrofuran (THF). 3.07 ml of triethylamine were added dropwise at 20° C., the mixture was stirred for 5 min, and 2.61 g (10 mmol) of (4′-chloro-4-methylbiphenyl-3-yl)acetic acid (EP 2029531 A1 and US 2009/298828 A1) were added. After 15 min, a further 2.3 ml of triethylamine were added, followed immediately by the dropwise addition of 0.58 ml (6.2 mmol) of phosphorus oxychloride, and the mixture was stirred under reflux for 30 min. The mixture was concentrated under reduced pressure and the residue was purified by means of flash chromatography on silica gel using the mobile phase n-hexane/ethyl acetate 1:1. This gave 3.6 g (73% of theory) of the title compound of melting point 186° C.

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