N-Methylaniline → HCID 11250127, compound

HRID 2120974Notes

Reaction equation

HRID 2120974 reaction equation
[CH2:1]([O:8][CH2:9][C@H:10]1[O:17][C@@H:14]([O:15][CH3:16])[C@H:13]([O:18]CC2C=CC(I)=CC=2)[C@@H:12]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][C:32]([Br:35])=[CH:31][CH:30]=2)[C@@H:11]1[O:36][CH2:37][C:38]1[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][CH:39]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CNC1C=CC=CC=1.CC([O-])(C)C.[Na+]>C1COCC1.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]>[CH2:1]([O:8][CH2:9][C@H:10]1[O:17][C@@H:14]([O:15][CH3:16])[C@H:13]([OH:18])[C@@H:12]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][C:32]([Br:35])=[CH:31][CH:30]=2)[C@@H:11]1[O:36][CH2:37][C:38]1[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][CH:39]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 7515N-MethylanilineHCID 11193634HCID 11193634, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 11250127HCID 11250127, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Glycoside 10 (0.138 g, 0.174 mmol) was loaded into a round-bottom flask and azeotropically dried with toluene (3×3 mL) followed by additional drying for 1 h under vacuum. The flask was purged with argon, N-methylaniline (20 μL, 0.182 mmol) was added and the residue dissolved in THF (0.60 mL). An oven-dried resealable Schlenk flask was evacuated and backfilled with argon. The flask was charged with Pd2dba3 (1.0 mol % Pd, 0.7 mg, 0.0008 mmol), 1-(N,N-dimethylamino)-1′-(dicyclohexylphosphino)biphenyl (1.0 mol %, 0.7 mg, 0.0017 mmol), NaOtBu (23.4 mg, 0.244 mmol), evacuated and backfilled with argon. A rubber septum was installed and glycoside/amine solution was added via cannula. The flask was sealed using a teflon screwcap and the reaction mixture was stirred at room temperature. After 4 h, the reaction solution was diluted with diethyl ether, filtered through a pad of celite and concentrated in vacuo. The aminated product was taken up in CH2Cl2 (1 mL) and treated with 2% dichloroacetic acid/CH2Cl2 (v/v) (1 mL). After stirring at room temperature for 30 min, the reaction mixture was diluted with CH2Cl2, washed with brine, saturated NaHCO3(aq), dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography on silica gel (20% EtOAc/Hexanes) gave 84.0 mg 11 (84%) as a white solid. [α]24D: −29.2° (c 2.19, CH2Cl2); IR (thin film) 3450, 2866, 1490, 1452, 1061 cm−1; 1H-NMR (CDCl3) δ 7.43 (d, J=8.2 Hz, 2H), 7.34-7.23 (m, 7H), 7.20 (d, J=8.2 Hz, 2H), 7.02 (d, J=8.5 Hz, 2H), 4.89 (d, J=11.6 Hz, 1H), 4.72 (d, J=11.6 Hz, 1H), 4.71 (d, J=11.0 Hz, 1H), 4.65 (d, J=12.2 Hz, 1H), 4.53 (d, J=12.2 Hz, 1H), 4.46 (d, J=11.0 Hz, 1H), 4.17 (d, J=7.6 Hz, 1H), 3.75-3.67 (m, 2H), 3.61-3.53 (m, 6H), 3.48-3.44 (m, 1H), 2.41 (d, J=1.5 Hz, 1H); 13C-NMR (CDCl3) δ 138.1, 137.7, 136.7, 133.7, 131.7, 129.6, 129.2, 128.7, 128.6, 128.1, 127.9, 121.7, 103.9, 84.5, 77.5, 75.2, 75.0, 74.4, 74.3, 73.7, 68.7, 57.4; FAB MS m/z (M+Na)+: calcd 599.0812, obsd 599.0795.

Workup

  1. dry with materialazeotropically dried with toluene (3×3 mL)
  2. customby additional drying for 1 h under vacuum
  3. additionwas added
  4. customAn oven-dried resealable Schlenk flask was evacuated
  5. customevacuated
  6. additionglycoside/amine solution was added via cannula
  7. customThe flask was sealed
  8. additionthe reaction solution was diluted with diethyl ether
  9. filtrationfiltered through a pad of celite
  10. concentrationconcentrated in vacuo
  11. additiontreated with 2% dichloroacetic acid/CH2Cl2 (v/v) (1 mL)
  12. stirringAfter stirring at room temperature for 30 min
  13. additionthe reaction mixture was diluted with CH2Cl2
  14. washwashed with brine, saturated NaHCO3(aq)
  15. dry with materialdried over Na2SO4
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo
  18. customPurification by flash column chromatography on silica gel (20% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-0168620ff80d4f09a019b5e3494c858d
Source dataset
uspto-grants-2004_02
Patent number
US06693178B2

Reaction notes

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