151103-09-2

基本信息
羅氟司特中間體1
羅氟司特-IM D
3-環(huán)丙甲氧基-4-二氟甲基苯甲醛
3-環(huán)己甲氧基-4-二氟甲氧基苯甲醛
3-(環(huán)丙甲氧基)-4-(二氟甲氧基)苯甲醛
4-(二氟甲氧基)-3-(環(huán)丙基甲氧基)苯甲
4-(二氟甲氧基)-3-(環(huán)丙基甲氧基)苯甲醛
3-(環(huán)丙基甲氧基)-4-(二氟甲氧基)苯甲醛
4-(二氟甲氧基)-3-(環(huán)丙基甲氧基)苯甲醛(羅氟司特中間體6)
3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzaldehyde
RofluMilast interMediate
RofluMilast InterMediate I
Intermediate Of Roflumilast
Benzaldehyde, 3-(cyclopropylMethoxy)-4
ROFLUMILAST INTERMEDIATE CAS 151103-09-2
4-(DIFLUOROMETHOXY)-3-(CYCLOPROPYLMETHOX...
3-CyclopropylMethoxy-4-isopropoxy-benzaldehyde
4-(DIFLUOROMETHOXY)-3-(CYCLOPROPYLMETHOXY)-BENZALD
物理化學(xué)性質(zhì)
制備方法

7051-34-5

151103-08-1

151103-09-2
以溴甲基環(huán)丙烷和4-二氟甲氧基-3-羥基苯甲醛為原料合成4-(二氟甲氧基)-3-(環(huán)丙基甲氧基)苯甲醛的一般步驟如下:將55g 4-(二氟甲氧基)-3-羥基苯甲醛、42.42g K2CO3(1.05當(dāng)量)、4.86g KI(0.1當(dāng)量)和220mL二甲基亞砜(DMSO)加入反應(yīng)器中。將混合物在70℃下加熱并攪拌1小時(shí)。隨后,緩慢滴加預(yù)先制備的42.65g溴甲基環(huán)丙烷(1.08當(dāng)量)和110mL DMSO的混合溶液,滴加時(shí)間控制在1小時(shí)。滴加完畢后,繼續(xù)在70℃下反應(yīng)3小時(shí)。反應(yīng)完成后,將反應(yīng)混合物冷卻至室溫。加入375mL甲苯稀釋反應(yīng)混合物,過濾以除去未反應(yīng)的K2CO3。將濾液冷卻至0-5℃,并加入375mL去離子水。分離有機(jī)相和水相,有機(jī)相用55mL去離子水洗滌兩次。最后,通過減壓蒸餾除去溶劑,得到70g(產(chǎn)率99%)的4-(二氟甲氧基)-3-(環(huán)丙基甲氧基)苯甲醛,為粘稠的淡黃色液體。
參考文獻(xiàn):
[1] Patent: WO2014/60464, 2014, A1. Location in patent: Page/Page column 15
[2] Patent: CN105254559, 2016, A. Location in patent: Paragraph 0041; 0042
[3] Patent: US2008/15226, 2008, A1. Location in patent: Page/Page column 10
[4] Patent: US2006/116373, 2006, A1. Location in patent: Page/Page column 6
[5] Organic and Biomolecular Chemistry, 2018, vol. 16, # 38, p. 6900 - 6908