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Cesium carbonate → (4S,5S)-4-(((tert-Butyldiphenylsilyl)oxy)methyl)-3-(6-chloro-2-morpholinopyrimidin-4-yl)-5-(4-methoxyphenyl)oxazolidin-2-one

HRID 929956
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HRID 929956 반응식
[Si:1]([O:18][CH2:19][C@H:20]1[C@H:24]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[O:23][C:22](=[O:33])[NH:21]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:34][C:35]1[CH:40]=[C:39](Cl)[N:38]=[C:37]([N:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)[N:36]=1.C([O-])([O-])=O.[Cs+].[Cs+].C([O-])(O)=O.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[Ar]>[Si:1]([O:18][CH2:19][C@H:20]1[C@H:24]([C:25]2[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=2)[O:23][C:22](=[O:33])[N:21]1[C:39]1[CH:40]=[C:35]([Cl:34])[N:36]=[C:37]([N:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)[N:38]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
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HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 27720684-(4,6-Dichloropyrimidin-2-yl)morpholineHCID 86718527(4S,5S)-4-(((tert-Butyldiphenylsilyl)oxy)methyl)-5-(4-methoxyphenyl)oxazolidin-2-one

생성물 1

HCID 86718539(4S,5S)-4-(((tert-Butyldiphenylsilyl)oxy)methyl)-3-(6-chloro-2-morpholinopyrimidin-4-yl)-5-(4-methoxyphenyl)oxazolidin-2-one
수율 99%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 86694355Argon 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene촉매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

To a solution of (4S,5S)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-5-(4-methoxyphenyl)-oxazolidin-2-one (1.65 g, 3.57 mmol), 4-(4,6-dichloropyrimidin-2-yl)morpholine (920 mg, 3.93 mmol) and Cs2CO3 (1.75 g, 5.36 mmol) in dioxane (20 mL) was added after purging with argon 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (145 mg, 250 μmol) and Pd2(dba)3 (65 mg, 0.071 mmol), and the reaction mixture was heated for 5 h at 100° C. The reaction mixture was added to 10% aqueous NaHCO3 solution and extracted with EtOAc. Combined extracts were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography using EtOAc in heptane from 0% to 50% in order to give the title compound as a white solid (2.33 g, 94%). TLC (heptane/EtOAc 1:1) Rf=0.52; LC-MS: [M+H] 659,661; Rt 1.58 min; (LCMS method 2). 1H NMR (400 MHz, CDCl3): 7.64 (m, 4H), 7.54 (s, 1H), 7.55-7.35 (m, 6H), 7.26 (m, 2H), 6.95 (d, 2H), 5.21 (d, 1H), 4.56 (m, 1H), 4.22 (dd, 1H), 3.96 (dd, 1H), 3.84 (s, 3H), 3.60-3.40 (m, 8H), 1.09 (s, 9H).

후처리

  1. extractionextracted with EtOAc
  2. washCombined extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography

출처 및 근거

ORD 기록
ord-c08dd7d65a58423082a34b704d5212a3
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09296733B2

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