反応 #162181

反応方程式

iPr2NEt

2,4-dichloro-5-fluoro-pyrimidine

methyl 5-(tert-butoxycarbonylamino)-1-methylcyclohexanecarboxylate

52g

methyl 5-(tert-butoxycarbonylamino)-1-methylcyclohexanecarboxylate

HCl

→

racemic product

(1R,3S)-methyl 3-(2-chloro-5-fluoropyrimidin-4-ylamino)-1-methyl-cyclohexanecarboxylate

溶媒

MeOH

反応条件

後処理

1. 1
   濃縮concentrated to dryness
2. 2
   workup.DISSOLUTIONredissolved in THF (50 mL)
3. 3
   workup.STIRRINGThe reaction was stirred
4. 4
   温度at reflux overnight
5. 5
   濃縮concentrated in vacuo
6. 6
   その他resulting residue
7. 7
   その他was purified by silica gel chromatography (1:1 Hexane:EtOAc)

実験手順

A stirred solution of methyl 5-(tert-butoxycarbonylamino)-1-methylcyclohexanecarboxylate, 52g, (5.63 g, 20.75 mmol) in MeOH (20 mL) was treated with HCl gas for 10 minutes. The resulting solution was stirred at room temperature for 1 hour, then concentrated to dryness and redissolved in THF (50 mL). To the reaction mixture was added iPr2NEt (10.84 mL, 62.25 mmol) and 2,4-dichloro-5-fluoro-pyrimidine (5.20 g, 31.12 mmol) sequentially. The reaction was stirred at reflux overnight, concentrated in vacuo and resulting residue was purified by silica gel chromatography (1:1 Hexane:EtOAc), yielding 2.2 g of the racemic product as a yellow oil. 300 mg of the racemic methyl 3-(2-chloro-5-fluoropyrimidin-4-ylamino)-1-methylcyclohexanecarboxylate was submitted for SFC chiral separation, yielding 100 mg of the desired product, 52h, as a yellow oil.

出典