Acetic Acid → HCID 86651616, compound

HRID 472680Notes

Reaction equation

HRID 472680 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>[F:56][C:2]([F:1])([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][CH2:32][C:33](=[O:38])[C:34]([O:36][CH3:37])=[O:35])([NH:24][S:25]([C:27]([CH3:29])([CH3:30])[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:11])([F:12])[F:10])[CH:8]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 25953Cesium fluorideHCID 516892Sodium BicarbonateHCID 86651614HCID 86651614, compound2×

Product 1

HCID 86651616HCID 86651616, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of Methyl 4-[(2R,4R)-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 5, 100 mg, 0.119 mmol) and Acetic acid (0.014 mL, 0.239 mmol) in Acetonitrile (2 mL) was added Cesium Fluoride (58.0 mg, 0.382 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 (64.4 mg, 0.089 mmol, 75% yield) as a white foam. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.97 (s, 1H) 7.58-7.72 (m, 2H) 7.08-7.22 (m, 1H) 6.88 (d, 1H) 6.70 (t, 1H) 5.25-5.38 (m, 1H) 5.03 (s, 1H) 4.35-4.50 (m, 1H) 3.72 (s, 3H) 2.86-3.22 (m, 4H) 2.65 (s, 3H) 2.36 (s, 3H) 1.44 (d, 3H) 1.32-2.12 (m, 6H) 1.19 (s, 9H). The sample consists of two species ratio ˜70:30 (see signals of OMe at 3.71 ppm, 3.66 ppm). UPLC: 2 peaks Rt 0.87 and 0.93 mins with the expected mass 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-37c35d6672814b4fb176dc92407e874e
Source dataset
uspto-grants-2014_01
Patent number
US08633214B2

Reaction notes

Loading…