Carbamic acid, 2-methylpropyl ester → HCID 21877961, compound

HRID 1991272Notes

Reaction equation

HRID 1991272 reaction equation
[S:1]1[CH2:6][CH:5]=[C:4]([C:7]2[C:12]([F:13])=[CH:11][C:10]([NH2:14])=[CH:9][C:8]=2[F:15])[CH2:3][CH2:2]1.C(=O)(O)[O-].[Na+].[C:21](=[O:28])([O:23][CH2:24][CH:25]([CH3:27])[CH3:26])N>C1COCC1.O>[CH2:24]([O:23][C:21](=[O:28])[NH:14][C:10]1[CH:9]=[C:8]([F:15])[C:7]([C:4]2[CH2:5][CH2:6][S:1][CH2:2][CH:3]=2)=[C:12]([F:13])[CH:11]=1)[CH:25]([CH3:27])[CH3:26]

Participants

5

Reactant 3

HCID 10973Carbamic acid, 2-methylpropyl esterHCID 516892Sodium BicarbonateHCID 21876582HCID 21876582, compound

Product 1

HCID 21877961HCID 21877961, compound

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a stirred, biphasic mixture of 4-(3,6-dihydro-2H-thiopyran-4-yl)-3,5-difluorobenzenamine (Step 4, 3.90 g, 17.2 mmol) in THF/water (2:1, 103 mL) is added sodium bicarbonate (2.88 g, 34.3 mmol) followed by isobutyl carbamate (2.45 mL, 18.9 mmol) dropwise. The reaction mixture is stirred at ambient temperature for 7 h and is then concentrated under reduced pressure, diluted with EtOAc (100 mL) and H2O (50 mL), and the layers are separated. The organic phase is washed with H2O (25 mL) and saline (25 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Purification of the residue by chromatography on a Biotage Flash 40M 90 g silica gel cartridge, eluting with 5-10% EtOAc/Hexanes, affords the title compound, mp 136-137° C.; MS (ESI−) for C16H19F2NO2S m/z 326 (M−H)−.

Workup

  1. concentrationis then concentrated under reduced pressure
  2. additiondiluted with EtOAc (100 mL) and H2O (50 mL)
  3. customthe layers are separated
  4. washThe organic phase is washed with H2O (25 mL) and saline (25 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customPurification of the residue by chromatography on a Biotage Flash 40M 90 g silica gel cartridge
  8. washeluting with 5-10% EtOAc/Hexanes

Sources & evidence

ORD record
ord-5ccce4c5b8cd4c2fa1c395de2c10c357
Source dataset
uspto-grants-2010_01
Patent number
US07645781B2

Reaction notes

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