Ethyl bromoacetate → HCID 69932817, compound

HRID 540794Notes

Reaction equation

HRID 540794 reaction equation
[F:1][C:2]([F:34])([F:33])[C:3]1[CH:32]=[CH:31][C:6]([O:7][C:8]2[NH:12][N:11]=[C:10]([C:13]3[CH:14]=[C:15]([C:19]4([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:22][O:21][CH2:20]4)[CH:16]=[CH:17][CH:18]=3)[CH:9]=2)=[CH:5][CH:4]=1.Br[CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCOC(C)=O>[F:34][C:2]([F:1])([F:33])[C:3]1[CH:32]=[CH:31][C:6]([O:7][C:8]2[CH:9]=[C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]4([NH:23][C:24]([O:25][C:26]([CH3:28])([CH3:29])[CH3:27])=[O:30])[CH2:22][O:21][CH2:20]4)[CH:14]=3)[N:11]([CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])[N:12]=2)=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 178452606HCID 178452606, compound

Product 1

HCID 69932817HCID 69932817, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyl {3-[3-(5-(4-trifluoromethylphenoxy)-1H-pyrazol-3-yl)phenyl]oxetan-3-yl}carbamate (98 mg, 0.21 mmol), ethyl bromoacetate (80 mg, 0.47 nimbi), and potassium carbonate (67 mg, 0.48 mmol) were combined in 0.5 mL of DMF and the mixture was stirred at ambient temperature under argon atmosphere for 4 h, then warmed to 60° C. for 18 h. The mixture was diluted with EtOAc and washed with water and brine. The organic phase was dried over MgSO4, filtered, and the solvent was removed under reduced pressure. The residue was chromatographed on a 12 g silica gel column using 0-5% MeOH:CHCl3 over 16 min at 30 mL/min. The fractions containing the first-eluting product were combined and evaporated under reduced pressure to give ethyl [3-(4-trifluoromethylphenoxy)-5-(3-{3-[(tert-butyloxycarbonyl)amino]oxetan-3-yl}phenyl)-1H-pyrazol-1-yl]acetate (product A) as an oil, calcd (M+1)+: 562.6. Found: 562.2. 1H NMR (400 MHz, CDCl3) δ 7.6 (m, 5H), 7.50 (t, J=7, 1H), 7.37 (d, J=7, 1H), 7.29 (s, 1H), 5.99 (s, 1H), 5.85 (br s, 1H), 5.00 (d, J=5, 2H), 4.85 (br d, 2H), 4.79 (s, 2H), 4.21 (q, J=7, 2H), 1.27 (t, J=7, 3H). The fractions containing the second-eluting product were combined and evaporated under reduced pressure to give ethyl [5-(4-trifluoromethylphenoxy)-3-(3-{3-[(tert-butyloxycarbonyl)amino]oxetan-3-yl}phenyl)-1H-pyrazol-1-yl]acetate (product B) as an oil, calcd (M+1)+: 562.6. Found: 562.9. 1H NMR (400 MHz, CDCl3) δ 7.88 (br s, 1H), 7.6 (m, 3H), 7.50 (d, J=7, 1H), 7.42 (t, J=7, 1H), 7.32 (d, J=6, 2H), 6.03 (s, 1H), 5.82 (br s, 1H), 5.00 (br s, 2H), 4.90 (overlapping brs s and sharp s, 4H), 4.21 (q, J=7, 2H), 1.25 (t, J=7, 3H).

Workup

  1. temperaturewarmed to 60° C. for 18 h
  2. washwashed with water and brine
  3. dry with materialThe organic phase was dried over MgSO4
  4. filtrationfiltered
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was chromatographed on a 12 g silica gel column
  7. waitCHCl3 over 16 min at 30 mL/min
  8. additionThe fractions containing the first-eluting product
  9. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-8589aee980d54ef1beb7072e0dec8265
Source dataset
uspto-grants-2014_10
Patent number
US08871796B2

Reaction notes

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