Cesium carbonate → tert-Butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(6-isopropoxy-1,1-dimethyl-3,4-dihydro-1H-isochromen-4-yl)amino]propylcarbamate

HRID 1296105

반응식

HRID 1296105 반응식
Br[CH:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH:13]([CH3:15])[CH3:14])[CH:10]=2)[C:5]([CH3:17])([CH3:16])[O:4][CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:24][CH2:25][C@@H:26]([OH:45])[C@@H:27]([NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41])[CH2:28][C:29]1[CH:34]=[C:33]([F:35])[CH:32]=[C:31]([F:36])[CH:30]=1>CN(C)C=O.C(OCC)(=O)C>[F:35][C:33]1[CH:34]=[C:29]([CH:30]=[C:31]([F:36])[CH:32]=1)[CH2:28][C@H:27]([NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41])[C@H:26]([OH:45])[CH2:25][NH:24][CH:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH:13]([CH3:15])[CH3:14])[CH:10]=2)[C:5]([CH3:17])([CH3:16])[O:4][CH2:3]1

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 58802335tert-butyl (1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamateHCID 589092714-bromo-6-isopropoxy-1,1-dimethyl-3,4-dihydro-1H-isochromene

생성물 1

HCID 58909444tert-Butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(6-isopropoxy-1,1-dimethyl-3,4-dihydro-1H-isochromen-4-yl)amino]propylcarbamate수율 47%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

A solution of 4-bromo-6-isopropoxy-1,1-dimethyl-3,4-dihydro-1H-isochromene (0.61 g, 2.04 mmol), cesium carbonate (1.33 g, 4.08 mmol), and tert-butyl (1S,2R)-3-amino-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate (0.64 g, 2.04 mmol) in N,N-dimethylformamide (10 mL) was stirred at 60° C., under nitrogen, for 24 h. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with 5% lithium chloride (3×40 mL), water (2×30 mL), saturated sodium chloride (30 mL), dried (sodium sulfate), and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica, 95:5 methylene chloride/methanol) to afford the desired product (0.51 g, 47%) as a pale-yellow foam: ESI MS m/z 535 [C29H40F2N2O5+H]+.

후처리

  1. washwashed with 5% lithium chloride (3×40 mL), water (2×30 mL), saturated sodium chloride (30 mL)
  2. dry with materialdried (sodium sulfate)
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by flash chromatography (silica, 95:5 methylene chloride/methanol)

출처 및 근거

ORD 기록
ord-c671f80389ea4a768737ec7341d63345
출처 데이터셋
uspto-grants-2007_07
특허 번호
US07244725B2

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