Potassium Carbonate → (S)-tert-butyl 4-(1-amino-1-oxo-3-(4'-(trifluoromethyl)biphenyl-4-yl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216904Notes

Reaction equation

HRID 216904 reaction equation
[NH2:1][C:2](=[O:29])[C@@H:3]([NH:12][C:13]([C:15]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](I)=[CH:7][CH:6]=1.[F:30][C:31]([F:42])([F:41])[C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.[CH2:43]([S:45]([C:48]1[CH:53]=[CH:52][C:51](B(O)O)=[CH:50][CH:49]=1)(=[O:47])=[O:46])[CH3:44].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[NH2:1][C:2](=[O:29])[C@@H:3]([NH:12][C:13]([C:15]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:35]2[CH:36]=[CH:37][C:32]([C:31]([F:42])([F:41])[F:30])=[CH:33][CH:34]=2)=[CH:7][CH:6]=1.[NH2:1][C:2](=[O:29])[C@@H:3]([NH:12][C:13]([C:15]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:51]2[CH:50]=[CH:49][C:48]([S:45]([CH2:43][CH3:44])(=[O:47])=[O:46])=[CH:53][CH:52]=2)=[CH:7][CH:6]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 27734204-(Ethylsulphonyl)benzeneboronic acidHCID 59568595(S)-tert-Butyl 4-(1-amino-3-(4-iodophenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Product 2

HCID 59568598(S)-tert-butyl 4-(1-amino-1-oxo-3-(4'-(trifluoromethyl)biphenyl-4-yl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamateHCID 59568601(S)-tert-butyl 4-(1-amino-3-(4'-(ethylsulfonyl)biphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

(S)-tert-Butyl 4-(1-amino-3-(4-iodophenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 1, step (iii), 2.0 g) in acetonitrile (5 mL) under nitrogen was treated with 4-(trifluoromethyl)phenylboronic acid (0.367 g) and 4-(ethylsulfonyl)phenylboronic acid (0.414 g) followed by aqueous potassium carbonate (3.87 mL) and 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (25 mg). The mixture was stirred at 75° C. for 18 h. The reaction mixture was evaporated, dissolved in dichloromethane, evaporated onto silica and purified on a silica column eluting with 50% ethyl acetate in isohexane and then 100% ethyl acetate to afford (S)-tert-butyl 4-(1-amino-1-oxo-3-(4′-(trifluoromethyl)biphenyl-4-yl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate and (S)-tert-butyl 4-(1-amino-3-(4′-(ethylsulfonyl)biphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate as a mixture (1.7 g).

Workup

  1. customThe reaction mixture was evaporated
  2. dissolutiondissolved in dichloromethane
  3. customevaporated onto silica
  4. custompurified on a silica column
  5. washeluting with 50% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-5e10018b5c9a4bfea64f98faff99416e
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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