1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 86651614, compound

HRID 472679Notes

Reaction equation

HRID 472679 reaction equation
N12CCCN=C1CCCCC2.[Cl-].[Li+].COP([CH:20]([O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[C:21]([O:23][CH3:24])=[O:22])(OC)=O.[F:33][C:34]([F:76])([F:75])[C:35]1[CH:36]=[C:37]([C@H:45]([N:47]([CH3:74])[C:48]([N:50]2[CH2:55][CH2:54][C@:53]([NH:59][S:60]([C:62]([CH3:65])([CH3:64])[CH3:63])=[O:61])([CH2:56][CH:57]=O)[CH2:52][C@@H:51]2[C:66]2[CH:71]=[CH:70][C:69]([F:72])=[CH:68][C:67]=2[CH3:73])=[O:49])[CH3:46])[CH:38]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:40]=1.C([O-])(O)=O.[Na+]>C(#N)C.CCOC(C)=O>[F:76][C:34]([F:33])([F:75])[C:35]1[CH:36]=[C:37]([C@H:45]([N:47]([CH3:74])[C:48]([N:50]2[CH2:55][CH2:54][C@@:53]([CH2:56][CH:57]=[C:20]([O:25][Si:26]([C:29]([CH3:30])([CH3:31])[CH3:32])([CH3:27])[CH3:28])[C:21]([O:23][CH3:24])=[O:22])([NH:59][S:60]([C:62]([CH3:65])([CH3:64])[CH3:63])=[O:61])[CH2:52][C@@H:51]2[C:66]2[CH:71]=[CH:70][C:69]([F:72])=[CH:68][C:67]=2[CH3:73])=[O:49])[CH3:46])[CH:38]=[C:39]([C:41]([F:42])([F:43])[F:44])[CH:40]=1

Participants

8

Reactant 5

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 433294Lithium ChlorideHCID 516892Sodium BicarbonateHCID 11077841HCID 11077841, compoundHCID 86651615HCID 86651615, compound2×

Product 1

HCID 86651614HCID 86651614, compoundYield 72.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

1,8-Diazabicyclo[5.4.0]undec-7-ene (0.185 mL, 1.24 mmol, Aldrich) was added dropwise to a suspension of Lithium chloride (55.6 mg, 1.31 mmol, Aldrich) and Methyl [bis(methyloxy)phosphoryl]{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}acetate (Tetrahedron Lett. 1981, 22, 663-666) (409 mg, 1.31 mmol) in dry Acetonitrile (20 mL) and the mixture was maintained at 0° C. for 1 h. A solution of (2R,4R)-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-4-{[(1,1-dimethylethyl)sulfinyl]amino}-2-(4-fluoro-2-methylphenyl)-N-methyl-4-(2-oxoethyl)-1-piperidinecarboxamide (Intermediate 4, 585 mg, 0.898 mmol) in Acetonitrile (5 mL) was added dropwise at 0° C. The mixture was stirred for 7 hours while the temperature was allowed to increase to 25° C. Saturated aqueous NaHCO3 and EtOAc were added to the reaction mixture and the two phases were separated. 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 (542 mg, 0.65 mmol, 72% yield) as a white solid.

Workup

  1. temperatureto increase to 25° C
  2. customthe two phases were separated
  3. dry with materialThe combined organic phases were dried (Na2SO4)
  4. customevaporated to dryness
  5. 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-466665f553b64c3791a8e21c0b6a44db
Source dataset
uspto-grants-2014_01
Patent number
US08633214B2

Reaction notes

Loading…