Acetic Acid → HCID 86684786, compound

HRID 472683Notes

Reaction equation

HRID 472683 reaction equation
[F:1][C:2]([F:56])([F:55])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:54])[C:16]([N:18]2[CH2:23][CH2:22][C@:21]([CH2:31][CH:32]=[C:33]([O:38][Si](C(C)(C)C)(C)C)[C:34]([O:36][CH3:37])=[O:35])([NH:24][S:25]([C:27]([CH3:30])([CH3:29])[CH3:28])=[O:26])[CH2:20][C@@H:19]2[C:46]2[CH:51]=[CH:50][C:49]([F:52])=[CH:48][C:47]=2[CH3:53])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(O)(=O)C.[F-].[Cs+].C([O-])(O)=O.[Na+]>C(#N)C>[CH3:37][O:36][C:34](=[O:35])[C:33](=[O:38])[CH2:32][CH2:31][C@:21]1([NH:24][S:25]([C:27]([CH3:29])([CH3:28])[CH3:30])=[O:26])[CH2:22][CH2:23][N:18]([C:16]([N:15]([C@@H:13]([C:5]2[CH:4]=[C:3]([C:2]([F:55])([F:56])[F:1])[CH:8]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:6]=2)[CH3:14])[CH3:54])=[O:17])[C@@H:19]([C:46]2[CH:51]=[CH:50][C:49]([F:52])=[CH:48][C:47]=2[CH3:53])[CH2:20]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 25953Cesium fluorideHCID 516892Sodium BicarbonateHCID 86684784HCID 86684784, compound2×

Product 1

HCID 86684786HCID 86684786, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of Methyl 4-[(2R,4S)-1-{[{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}(methyl)amino]carbonyl}-4-{[(1,1-dimethylethyl)sulfinyl]amino}-2-(4-fluoro-2-methylphenyl)-4-piperidinyl]-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2-butenoate (Intermediate 10, 184 mg, 0.220 mmol) and Acetic acid (0.025 mL, 0.439 mmol) in Acetonitrile (4 mL) was added Cesium Fluoride (107 mg, 0.703 mmol, Aldrich) and the reaction mixture was stirred at 25° C. for 5 hrs. NaHCO3 saturated solution was added very carefully and the mixture was extracted with EtOAc (3×). The combined organic phases were dried (Na2SO4) and evaporated to dryness. The crude was purified by flash chromatography on silica with SP1 (Biotage) system (from 1:0 to 0:1 Cyclohexane/EtOAc) to give the title compound (108 mg, 0.149 mmol, 68% yield) as a colourless oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.92-8.03 (m, 1H) 7.62-7.75 (m, 2H) 6.68-7.30 (m, 3H) 5.20-5.37 (m, 1H) 4.94-5.07 (m, 1H) 4.30-4.46 (m, 1H) 3.67-3.81 (m, 3H) 2.86-3.07 (m, 2H) 1.58-2.77 (m, 14H) 1.45-1.53 (m, 3H) 1.03-1.12 (m, 9H). Mixture of two species (see the signals of OMe at 3.77 ppm, 3.70 ppm). UPLC: 2 peaks Rt 0.87 and 0.93 mins, m/z=724 [M+H]+.

Workup

  1. extractionthe mixture was extracted with EtOAc (3×)
  2. dry with materialThe combined organic phases were dried (Na2SO4)
  3. customevaporated to dryness
  4. customThe crude was purified by flash chromatography on silica with SP1 (Biotage) system (from 1:0 to 0:1 Cyclohexane/EtOAc)

Sources & evidence

ORD record
ord-9c9e9ea000d14aa4bdf6310e857a5a39
Source dataset
uspto-grants-2014_01
Patent number
US08633214B2

Reaction notes

Loading…