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Cesium carbonate → (R)-tert-butyl (3-hydroxy-3-(3-((tetrahydro-2H-pyran-4-yl)methoxy)phenyl)propyl)carbamate

HRID 2277042
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HRID 2277042 반응식
C([O-])([O-])=O.[Cs+].[Cs+].CS([O:11][CH2:12][CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)(=O)=O.[OH:19][C@@H:20]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33](O)[CH:32]=1)[CH2:21][CH2:22][NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27].[NH4+].[Cl-]>CN(C=O)C>[OH:19][C@@H:20]([C:31]1[CH:32]=[CH:33][CH:34]=[C:35]([O:11][CH2:12][CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[CH:36]=1)[CH2:21][CH2:22][NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27]
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참가 물질

6

반응물 4

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 15166436Oxan-4-ylmethyl methanesulfonateHCID 90405310(R)-tert-butyl 3-hydroxy-3-(3-hydroxyphenyl)propylcarbamate

생성물 1

HCID 90448349(R)-tert-butyl (3-hydroxy-3-(3-((tetrahydro-2H-pyran-4-yl)methoxy)phenyl)propyl)carbamate

시약·촉매·용매 1

HCID 6228
Dimethylformamide
용매

실험 절차

Cs2CO3 (2.34 g, 7.18 mmol) was added to a solution of (tetrahydro-2H-pyran-4-yl)methyl methanesulfonate (1.05 g, 5.41 mmol) and Intermediate I (1.13 g, 4.23 mmol) in anhydrous DMF (11 mL) and the reaction mixture was heated at +70° C. under Ar for 22 hrs. Aqueous NH4Cl (25%) was added and the reaction mixture was extracted with MTBE twice. Combined organic layers were washed with brine, concentrated under reduced pressure. Purification by flash chromatography (25%-100% EtOAc-hexanes gradient) gave (R)-tert-butyl (3-hydroxy-3-(3-((tetrahydro-2H-pyran-4-yl)methoxy)phenyl)propyl)carbamate as a colorless oil. Yield (0.47 g, 30%); 1H NMR (400 MHz, DMSO-d6) δ 7.18 (t, J=8.0 Hz, 1H), 6.85-6.84 (m, 2H), 6.76-6.74 (m, 2H), 5.15 (d, J=4.4 Hz, 1H), 4.49 (q, J=4.4 Hz, 1H), 3.88-3.84 (m, 2H), 3.79 (d, J=6.4 Hz, 2H), 2.94 (q, J=6.4 Hz, 2H), 1.70-1.62 (m, 4H), 1.38-1.26 (m, 11H).

후처리

  1. temperaturethe reaction mixture was heated at +70° C. under Ar for 22 hrs
  2. extractionthe reaction mixture was extracted with MTBE twice
  3. washCombined organic layers were washed with brine
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash chromatography (25%-100% EtOAc-hexanes gradient)

출처 및 근거

ORD 기록
ord-5cd105993c4c4d4692882a051c192864
출처 데이터셋
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09133154B2

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