Bromobenzene → HCID 59031031, compound

HRID 1442657Notes

Reaction equation

HRID 1442657 reaction equation
[CH:1]1([N:4]([CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[C:5](=[O:19])[C:6]2[CH:11]=[CH:10][C:9]([C@@:12]([OH:18])([CH3:17])[C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=2)[CH2:3][CH2:2]1.Br[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(O[Na])(C)(C)C.CCOC(C)=O>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:1]1([N:4]([CH:20]2[CH2:21][CH2:22][N:23]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:24][CH2:25]2)[C:5](=[O:19])[C:6]2[CH:11]=[CH:10][C:9]([C@@:12]([OH:18])([CH3:17])[C:13]([F:16])([F:15])[F:14])=[CH:8][CH:7]=2)[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 7961BromobenzeneHCID 8857Ethyl AcetateHCID 59031023HCID 59031023, compoundHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 59031031HCID 59031031, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of (S)-N-cyclopropyl-N-(piperidin-4-yl)-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzamide prepared above in step c in Example 1 (43 mg, 0.12 mmol, 1.0 equiv.), bromobenzene (15 μL, 0.14 mmol, 1.2 equiv.), (±)-BINAP (6.7 mg, 0.011 mmol, 0.09 equiv.), and t-BuONa (28 mg, 0.29 mmol, 2.4 equiv.) in toluene (150 μL, degassed by Argon for 10 min) was treated with Pd2(dba)3 (3.3 mg, 0.0036 mmol, 0.03 equiv.) under Argon. After being stirred for 17 h at 80° C. under argon, the reaction was diluted (EtOAc) and washed (brine). The organic layer was dried (Na2SO4) and concentrated under reduced pressure. Purification of the residue by flash chromatography (SiO2, 20-50% EtOAc/Hexanes, gradient elution) gave the title compound as a pale yellow solid: 1H NMR (CDCl3, 500 MHz) δ 7.59 (d, J=8.3 Hz, 2H), 7.50 (d, J=8.5 Hz, 2H), 7.28-7.25 (m, 2H), 6.98-6.96 (m, 2H), 6.88-6.85 (m, 1H), 4.35-4.25 (m, 1H), 3.80-3.75 (m, 2H), 2.87-2.82 (m, 2H), 2.62-2.54 (m, 1H), 2.52 (s, 1H), 2.28-2.21 (m, 2H), 2.04-2.00 (m, 2H), 1.80 (s, 3H), 0.60-0.57 (m, 2H), 0.49-0.45 (m, 2H); MS(ESI) 433 [M+H]+.

Workup

  1. washwashed (brine)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customPurification of the residue
  5. washby flash chromatography (SiO2, 20-50% EtOAc/Hexanes, gradient elution)

Sources & evidence

ORD record
ord-1e8db7a67d4b4554a460a4d0649e7458
Source dataset
uspto-grants-2010_02
Patent number
US07659287B2

Reaction notes

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