Ethyl Acetate → Ethyl 4-{2-[benzyloxycarbonyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yloxy}-butyrate

HRID 604206Notes

Reaction equation

HRID 604206 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[CH2:6][N:7]([C:18]1[N:23]=[CH:22][C:21]([OH:24])=[CH:20][N:19]=1)[C:8](=[O:17])[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.Br[CH2:35][CH2:36][CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C)C=O>[CH2:10]([O:9][C:8]([N:7]([CH2:6][C:5]1[CH:4]=[C:3]([C:2]([F:1])([F:32])[F:33])[CH:27]=[C:26]([C:28]([F:29])([F:30])[F:31])[CH:25]=1)[C:18]1[N:19]=[CH:20][C:21]([O:24][CH2:35][CH2:36][CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:22][N:23]=1)=[O:17])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 76300Ethyl 4-bromobutyrateHCID 86626519Benzyl (3,5-bis-trifluoromethyl-benzyl)-(5-hydroxy-pyrimidin-2-yl)-carbamate

Product 1

HCID 86626520Ethyl 4-{2-[benzyloxycarbonyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yloxy}-butyrateYield 78.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Benzyl (3,5-bis-trifluoromethyl-benzyl)-(5-hydroxy-pyrimidin-2-yl)-carbamate (9.70 g) and ethyl 4-bromobutyrate (3.53 g) are dissolved in N,N-dimethylformamide (50 mL) and thereto is added potassium carbonate (3.41 g) and the mixture is stirred at 50° C. for 1 hour. Thereto are added ethyl acetate and a saturated brine, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:1) to give ethyl 4-{2-[benzyloxycarbonyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yloxy}-butyrate (8.29 g). MS (m/z): 586 [M+H]+

Workup

  1. customa saturated brine, and the mixture is separated
  2. washthe organic layer is washed with a saturated brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:1)

Sources & evidence

ORD record
ord-2c6d2a6694a540e3aeb38928fda1ca73
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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