Pivalic acid → 4-(5-(4-(Heptyloxy)phenyl)thiazol-2-yl)benzaldehyde

HRID 716404Notes

Reaction equation

HRID 716404 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[CH:8][CH:7]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C(O)(=O)C(C)(C)C.C(=O)([O-])[O-].[K+].[K+].Br[C:47]1[CH:52]=[CH:51][C:50]([O:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH3:60])=[CH:49][CH:48]=1>CC(N(C)C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:54]([O:53][C:50]1[CH:49]=[CH:48][C:47]([C:5]2[S:1][C:2]([C:6]3[CH:7]=[CH:8][C:9]([CH:10]=[O:11])=[CH:12][CH:13]=3)=[N:3][CH:4]=2)=[CH:52][CH:51]=1)[CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH3:60]

Participants

8

Reactant 5

HCID 6417Pivalic acidHCID 11430Potassium CarbonateHCID 75806TricyclohexylphosphineHCID 5991021-(4-Bromophenoxy)heptaneHCID 105356554-(1,3-Thiazol-2-yl)benzaldehyde

Product 1

HCID 866896684-(5-(4-(Heptyloxy)phenyl)thiazol-2-yl)benzaldehydeYield 38.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
100 °C

Procedure

To a stirring suspension of 4-(thiazol-2-yl)benzaldehyde (349 mg, 1.84 mmol), tricyclohexylphosphine (27 mg, 0.07 mmol), pivalic acid (64.2 μl, 0.55 mmol), potassium carbonate (382 mg, 2.77 mmol) and palladium (II) acetate (8 mg, 0.04 mmol) in DMA (5.15 mL) under nitrogen was added a solution of 1-bromo-4-(heptyloxy)benzene (500 mg, 1.84 mmol) in DMA (1 mL). The reaction mixture was evacuated and purged with nitrogen 3 times then heated at 100° C. for 6 h. Once cooled, the reaction mixture was diluted with EA (40 mL), washed with water (3×40 mL) and brine (40 mL). The organic phase was dried over MgSO4, filtered and concentrated in vacuo to afford a brown-green solid. The crude product was purified by chromatography (0-50% EA in hexanes) to afford 270 mg (37%) of 4-(5-(4-(heptyloxy)phenyl)thiazol-2-yl)benzaldehyde as an iridescent yellow solid. LCMS-ESI (m/z) calculated for C23H25NO2S: 379.5. found 380.0 [M+H]+, tR=2.99 min. (Method 8).

Workup

  1. customThe reaction mixture was evacuated
  2. custompurged with nitrogen 3 times
  3. temperatureOnce cooled
  4. additionthe reaction mixture was diluted with EA (40 mL)
  5. washwashed with water (3×40 mL) and brine (40 mL)
  6. dry with materialThe organic phase was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford a brown-green solid
  10. customThe crude product was purified by chromatography (0-50% EA in hexanes)

Sources & evidence

ORD record
ord-6314c09ef8654f6cb382e5359f1be58f
Source dataset
uspto-grants-2015_11
Patent number
US09187522B2

Reaction notes

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