Cesium carbonate → tert-butyl ((3R)-3-hydroxy-3-(3-((6-oxopiperidin-2-yl)methoxy)phenyl)propyl)carbamate

HRID 2277071Notes

Reaction equation

HRID 2277071 reaction equation
CS([O:5][CH2:6][CH:7]1[CH2:12][CH2:11][CH2:10][C:9](=[O:13])[NH:8]1)(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+].[OH:20][C@@H:21]([C:32]1[CH:37]=[CH:36][CH:35]=[C:34](O)[CH:33]=1)[CH2:22][CH2:23][NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28]>CN(C=O)C>[OH:20][C@@H:21]([C:32]1[CH:33]=[CH:34][CH:35]=[C:36]([O:5][CH2:6][CH:7]2[CH2:12][CH2:11][CH2:10][C:9](=[O:13])[NH:8]2)[CH:37]=1)[CH2:22][CH2:23][NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 90404452(6-Oxopiperidin-2-yl)methyl methanesulfonateHCID 90405310(R)-tert-butyl 3-hydroxy-3-(3-hydroxyphenyl)propylcarbamate2×

Product 1

HCID 131733447tert-butyl ((3R)-3-hydroxy-3-(3-((6-oxopiperidin-2-yl)methoxy)phenyl)propyl)carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of (6-oxopiperidin-2-yl)methyl methanesulfonate (0.44 g, 2.2 mmol) in DMF (15 ml) was added Cs2CO3 (3.5 g, 11 mmol) and phenol (Intermediate I) (0.88 g, 3.3 mmol). The reaction mixture was stirred at room temperature for 40 hours and partitioned between water and ethyl acetate. Organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography (20% MeOH-EtOAc) gave tert-butyl ((3R)-3-hydroxy-3-(3-((6-oxopiperidin-2-yl)methoxy)phenyl)propyl)carbamate as a yellow oil. Yield (0.17 g, 20%); 1H NMR (400 MHz, CD3OD) δ 7.24 (t, J=8.0 Hz, 1H), 6.97-6.93 (m, 2H), 6.84 (d, J=8.0 Hz, 1H), 4.64 (t, J=7.2 Hz, 1H), 4.06-4.02 (m, 1H), 3.94-3.90 (m, 1H), 3.86-3.76 (m, 1H), 3.15-3.06 (m, 2H), 2.37-2.30 (m, 2H), 2.05-1.92 (m, 3H), 1.86-1.75 (m, 3H), 1.43 (s, 9H).

Workup

  1. custompartitioned between water and ethyl acetate
  2. washOrganic layer was washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash chromatography (20% MeOH-EtOAc)

Sources & evidence

ORD record
ord-808a63fdd61a4ac3b35e8742dff2be1d
Source dataset
uspto-grants-2015_09
Patent number
US09133154B2

Reaction notes

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