Cesium carbonate → HCID 16222230, 화합물

HRID 1710877노트

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HRID 1710877 반응식
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([C:12]([O:14][CH3:15])=[O:13])[N:7]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:6][CH2:5]2.Br[CH2:24][C:25]1[C:30]([F:31])=[C:29]([Cl:32])[CH:28]=[CH:27][C:26]=1[F:33].C([O-])([O-])=O.[Cs+].[Cs+]>CC(C)=O>[Cl:32][C:29]1[C:30]([F:31])=[C:25]([C:26]([F:33])=[CH:27][CH:28]=1)[CH2:24][O:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([C:12]([O:14][CH3:15])=[O:13])[N:7]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:6][CH2:5]2

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 27735502-(Bromomethyl)-4-chloro-1,3-difluorobenzeneHCID 58858237(R)-2-tert-butyl 1-methyl 6-hydroxy-3,4-dihydroisoquinoline-1,2(1H)-dicarboxylate

생성물 1

HCID 16222230HCID 16222230, 화합물수율 97%

시약·촉매·용매 1

HCID 180Acetone용매

실험 절차

To a solution of (R)-2-tert-butyl 1-methyl 6-hydroxy-3,4-dihydroisoquinoline-1,2(1H)-dicarboxylate (1.1 g, 3.58 mmol) in acetone (10 mL) was added 2-(bromomethyl)-4-chloro-1,3-difluorobenzene (0.95 g, 3.94 mmol) followed by the addition of Cs2CO3 (1.28 g, 3.94 mmol). The reaction was stirred at room temperature for 3.5 h and filtered. The solid was rinsed by CH2Cl2 several times. The combined organic layers and filtrate were concentrated and purified by column chromatography on ISCO (40 g) with 0-30% ethyl acetate in hexanes over 25 minutes to yield (R)-2-tert-butyl 1-methyl 6-(3-chloro-2,6-difluorobenzyloxy)-3,4-dihydroisoquinoline-1,2(1H)-dicarboxylate as a white foam (1.62 g, 97%). HPLC retention time (Method C)=4.18 min. LC/MS (ESI) (M+H−Boc)+=368.1. 1H NMR (400 MHz, CDCl3) δ ppm 1.48 (d, J=9.67 Hz, 9H), 2.71-2.88 (m, 1H), 2.88-3.07 (m, 1H), 3.70 (s, 4H), 3.72-3.85 (m, 2H), 5.10 (s, 2H), 6.78 (s, 1H), 6.86 (dd, J=8.79, 2.64 Hz, 1H), 6.89-6.97 (m, 1H), 7.33-7.46 (m, 2H).

후처리

  1. filtrationfiltered
  2. washThe solid was rinsed by CH2Cl2 several times
  3. concentrationThe combined organic layers and filtrate were concentrated
  4. custompurified by column chromatography on ISCO (40 g) with 0-30% ethyl acetate in hexanes over 25 minutes

출처 및 근거

ORD 기록
ord-fff37581f633453a8d9903eefb891435
출처 데이터셋
uspto-grants-2010_09
특허 번호
US07790745B2

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