Sodium Hydroxide → HCID 86642507, compound

HRID 421216Notes

Reaction equation

HRID 421216 reaction equation
[CH3:1][C:2]([Si:5]([CH3:18])([CH3:17])[O:6][CH2:7][C@@H:8]1[NH:13][CH2:12][CH2:11][N:10]2[CH2:14][CH2:15][CH2:16][C@@H:9]12)([CH3:4])[CH3:3].[F:19][C:20]([F:54])([F:53])[C:21]1[CH:22]=[C:23]([C:31]([CH3:52])([CH3:51])[C:32]([N:34]([C:36]2[CH:37]=[N:38][C:39](Cl)=[CH:40][C:41]=2[C:42]2[CH:47]=[CH:46][C:45]([F:48])=[CH:44][C:43]=2[CH3:49])[CH3:35])=[O:33])[CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1.[OH-].[Na+]>C1(C)C=CC=CC=1.[Cl-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[F:30][C:27]([F:28])([F:29])[C:25]1[CH:24]=[C:23]([C:31]([CH3:52])([CH3:51])[C:32]([N:34]([C:36]2[CH:37]=[N:38][C:39]([N:13]3[CH2:12][CH2:11][N:10]4[CH2:14][CH2:15][CH2:16][C@H:9]4[C@@H:8]3[CH2:7][O:6][Si:5]([C:2]([CH3:1])([CH3:3])[CH3:4])([CH3:18])[CH3:17])=[CH:40][C:41]=2[C:42]2[CH:47]=[CH:46][C:45]([F:48])=[CH:44][C:43]=2[CH3:49])[CH3:35])=[O:33])[CH:22]=[C:21]([C:20]([F:54])([F:19])[F:53])[CH:26]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 235027842-(3,5-Bis(trifluoromethyl)phenyl)-N-(6-chloro-4-(4-fluoro-2-methylphenyl)pyrid-3-yl)-N,2-dimethylpropanamideHCID 66658730HCID 66658730, compound

Product 1

HCID 86642507HCID 86642507, compoundYield 9.7%

Reagents, catalysts & solvents 3

HCID 8154Hexadecyltrimethylammonium chlorideCatalystHCID 2734558Bis(tri-tert-butylphosphine)palladium(0)CatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
90 °C

Procedure

To a solution of cis-1-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)octahydropyrrolo[1,2-a]pyrazine (D73, 50 mg) in dry toluene (0.5 mL), a solution of 2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-chloro-4-(4-fluoro-2-methylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide [WO 2005/002577] (75 mg) in dry toluene (0.5 mL) was added at rt. Hexadecyltrimethylammonium chloride (25% aqueous solution, 132 microL), bis(tri-tert-butyl phosphine) palladium (19 mg) and NaOH (50% aqueous solution, 245 microL) were added. The resulting mixture was degassed by two freeze-thaw cycles and allowed to reach rt under a nitrogen atmosphere. The mixture was then heated at 90° C. for 5 hours. The mixture was allowed to cool down to rt, diluted with ethyl acetate (1 mL) and washed with a saturated solution of NaHCO3 (1 mL). The aqueous phase was extracted with ethyl acetate (3×2.5 mL). The combined organic extracts were dried and concentrated in vacuo to a residue which was purified by flash chromatography (Cycl/EtOAc 1:1) to give the desired compound (10.5 mg) as yellow oil.

Workup

  1. customThe resulting mixture was degassed by two freeze-thaw cycles
  2. customto reach rt under a nitrogen atmosphere
  3. temperatureto cool down to rt
  4. additiondiluted with ethyl acetate (1 mL)
  5. washwashed with a saturated solution of NaHCO3 (1 mL)
  6. extractionThe aqueous phase was extracted with ethyl acetate (3×2.5 mL)
  7. customThe combined organic extracts were dried
  8. concentrationconcentrated in vacuo to a residue which
  9. customwas purified by flash chromatography (Cycl/EtOAc 1:1)

Sources & evidence

ORD record
ord-9586b5fa2bc941efbf75a1d8e241cee3
Source dataset
uspto-grants-2012_01
Patent number
US08097618B2

Reaction notes

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