P-Anisidine → 4-(3-(tert-butyldimethylsilyloxy)propoxy)-N-(4-methoxyphenyl)aniline

HRID 84996Notes

Reaction equation

HRID 84996 reaction equation
Br[C:2]1[CH:19]=[CH:18][C:5]([O:6][CH2:7][CH2:8][CH2:9][O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])=[CH:4][CH:3]=1.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([NH2:28])=[CH:24][CH:23]=1.CC(C)([O-])C.[Na+]>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1(C)C=CC=CC=1>[Si:11]([O:10][CH2:9][CH2:8][CH2:7][O:6][C:5]1[CH:18]=[CH:19][C:2]([NH:28][C:25]2[CH:26]=[CH:27][C:22]([O:21][CH3:20])=[CH:23][CH:24]=2)=[CH:3][CH:4]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 7732P-AnisidineHCID 23676156Sodium t-butoxideHCID 58452906HCID 58452906, compound

Product 1

HCID 667303054-(3-(tert-butyldimethylsilyloxy)propoxy)-N-(4-methoxyphenyl)aniline

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 1140TolueneSolvent3×

Conditions

Temperature
90 °C

Procedure

5. To a dry 500 mL round bottom flask under nitrogen was added (3-(4-bromophenoxy)propoxy)(tert-butyl)dimethylsilane (12.1 g, 35.0 mmol), 4-anisidine (5.17 g, 42.0 mmol), and 20 mL anhydrous toluene. The mixture was degassed for 10 minutes before addition of dibenzylideneacetone di palladium Pd2(dba)3 (0.64 g, 0.70 mmol), 1,1′-Bis(diphenylphosphino)ferrocene (DPPF) (0.68 g, 1.2 mmol), and 20 mL anhydrous toluene. After 10 minutes of mixing, sodium tert-butoxide (4.7 g, 49.0 mmol) was added with 10 mL anhydrous toluene. The reaction mixture was heated to 90° C. and allowed to stir overnight while being monitored by thin layer chromatography. Upon disappearance of the starting material the reaction mixture was filtered through a plug of silica gel eluting with dichloromethane (Reaction Time=22 h). The product was purified by flash chromatography (silica gel, 5:1 hexanes:ethyl acetate). The solvent was removed under reduced pressure. The residual solvent was removed in vacuo (11.3 g, 83.0%). 1H NMR (300 MHz, CDCl3) δ 7.06 (d, J=3.3 Hz, 2H), 7.03 (d, J=3.3 Hz, 2H), 6.91 (d, J=3.3 Hz, 2H), 6.88 (d, J=3.3 Hz, 2H), 6.85 (s, 1H), 4.10 (t, 6.3 Hz, 2H), 3.90 (t, J=6.0 Hz, 2H), 3.81 (s, 3H), 2.01 (q, J=6.3 Hz, 2H), 0.97 (s, 9H), 0.14 (s, 6H).

Workup

  1. additionAfter 10 minutes of mixing
  2. filtrationUpon disappearance of the starting material the reaction mixture was filtered through a plug of silica gel eluting with dichloromethane (Reaction Time=22 h)
  3. customThe product was purified by flash chromatography (silica gel, 5:1 hexanes:ethyl acetate)
  4. customThe solvent was removed under reduced pressure
  5. customThe residual solvent was removed in vacuo (11.3 g, 83.0%)

Sources & evidence

ORD record
ord-387cb399791743a4a5baa195d6203ab6
Source dataset
uspto-grants-2014_09
Patent number
US08846978B2

Reaction notes

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