Iodoethane → Tert-butyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(4-ethoxy-5'-isopropyl-2'-methoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate

HRID 604193Notes

Reaction equation

HRID 604193 reaction equation
[F:1][C:2]([F:52])([F:51])[C:3]1[CH:4]=[C:5]([CH:44]=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:46]=1)[CH2:6][N:7]([CH2:25][C:26]1[CH:31]=[C:30]([OH:32])[CH:29]=[CH:28][C:27]=1[C:33]1[CH:38]=[C:37]([CH:39]([CH3:41])[CH3:40])[CH:36]=[CH:35][C:34]=1[O:42][CH3:43])[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:10][N:9]=1.C(=O)([O-])[O-].[K+].[K+].I[CH2:60][CH3:61].C(OCC)(=O)C>CN(C)C=O>[F:52][C:2]([F:1])([F:51])[C:3]1[CH:4]=[C:5]([CH:44]=[C:45]([C:47]([F:48])([F:49])[F:50])[CH:46]=1)[CH2:6][N:7]([CH2:25][C:26]1[CH:31]=[C:30]([O:32][CH2:60][CH3:61])[CH:29]=[CH:28][C:27]=1[C:33]1[CH:38]=[C:37]([CH:39]([CH3:41])[CH3:40])[CH:36]=[CH:35][C:34]=1[O:42][CH3:43])[C:8]1[N:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])=[CH:12][N:13]=1

Participants

6

Reactant 4

HCID 6340IodoethaneHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 86626921Tert-butyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(4-hydroxy-5'-isopropyl-2'-methoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate

Product 1

HCID 86626922Tert-butyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(4-ethoxy-5'-isopropyl-2'-methoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrateYield 83.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Tert-butyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(4-hydroxy-5′-isopropyl-2′-methoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate (70 mg) is dissolved in N,N-dimethylformamide (3 ml) and thereto are added potassium carbonate (26.4 mg) and iodoethane (29.8 mg) and the mixture is stirred at 50° C. for 8 hours. Thereto are added ethyl acetate and a water, 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 NH-silica gel column chromatography (hexane:ethyl acetate=1:0→9:1) to give tert-butyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(4-ethoxy-5′-isopropyl-2′-methoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate (60.5 mg). MS (m/z): 762 [M+H]+

Workup

  1. customa water, 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 NH-silica gel column chromatography (hexane:ethyl acetate=1:0→9:1)

Sources & evidence

ORD record
ord-3ea5afb3e74d464aa9ec83dc09cc0bda
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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