Sodium hydride → 4-(6-Chloro-2-oxo-2H-chromen-4-ylamino)-3,3-dimethyl-piperidine-1-carboxylic acid ethyl ester

HRID 897264Notes

Reaction equation

HRID 897264 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][CH:9]([NH2:12])[C:8]([CH3:14])([CH3:13])[CH2:7]1)=[O:5])[CH3:2].[H-].[Na+].[Cl:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[O:24][C:23](=[O:28])[CH:22]=[C:21]2OS(C(F)(F)F)(=O)=O>CN(C=O)C>[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][CH:9]([NH:12][C:21]2[C:20]3[C:25](=[CH:26][CH:27]=[C:18]([Cl:17])[CH:19]=3)[O:24][C:23](=[O:28])[CH:22]=2)[C:8]([CH3:13])([CH3:14])[CH2:7]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 101713244-Amino-3,3-dimethyl-piperidine-1-carboxylic acid ethyl esterHCID 20817849HCID 20817849, compound

Product 1

HCID 865926364-(6-Chloro-2-oxo-2H-chromen-4-ylamino)-3,3-dimethyl-piperidine-1-carboxylic acid ethyl esterYield 60.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of the 4-amino-3,3-dimethyl-piperidine-1-carboxylic acid ethyl ester (131 mg, 0.654 mmol) in DMF was added NaH (36.4 mg, 0.910 mmol) under nitrogen, and the mixture was stirred 10 min before trifluoro-methanesulfonic acid 6-chloro-2-oxo-2H-chromen-4-yl ester (prepared as before, 184 mg, 0.519 mmol) in DMF was added slowly, dropwise. The mixture was stirred 3 d before being concentrated with nitrogen flow to about half its original volume. The mixture was partitioned between EtOAc and H2O and the layers were separated. The aqueous was extracted with EtOAc (3×) and the combined organics were washed with H2O, saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated in vacuo. Silica gel chromatography eluting with a gradient of 0 to 5% MeOH in CH2Cl2 afforded 119 mg (56%) of the title compound as a yellow solid. MS (ESI(+)Q1MS) m/z 379 (M+H)+; 1H NMR (300 MHz, DMSO) δ ppm 0.83-0.93 (m, 6H), 1.19 (t, 3H, J=7.0 Hz), 1.50-1.63 (m, 1H), 1.70-1.91 (m, 1H), 2.67-3.07 (m, 2H), 3.58-3.84 (m, 2H), 3.92-4.14 (m, 3H), 5.55 (s, 1H), 6.77-6.88 (m, 1H), 7.30-7.40 (m, 1H), 7.60-7.69 (m, 1H), 8.40-8.48 (m, 1H).

Workup

  1. additionwas added slowly
  2. concentrationbefore being concentrated with nitrogen flow to about half its original volume
  3. customThe mixture was partitioned between EtOAc and H2O
  4. customthe layers were separated
  5. extractionThe aqueous was extracted with EtOAc (3×)
  6. washthe combined organics were washed with H2O, saturated aqueous NaCl
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. washSilica gel chromatography eluting with a gradient of 0 to 5% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-5c842ec0b03a47bc9b8daec4478f5405
Source dataset
uspto-grants-2005_07
Patent number
US06921821B2

Reaction notes

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