Water → N-[3-(2-Benzyl-2-aza-bicyclo[3.3.1]non-5-yl)-phenyl]-methanesulfonamide

HRID 1827941Notes

Reaction equation

HRID 1827941 reaction equation
[CH2:1]([N:8]1[CH2:15][CH2:14][C:13]2([C:17]3[CH:18]=[C:19]([NH2:23])[CH:20]=[CH:21][CH:22]=3)[CH2:16][CH:9]1[CH2:10][CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:24][S:25](Cl)(=[O:27])=[O:26].O>N1C=CC=CC=1.C1(C)C=CC=CC=1>[CH2:1]([N:8]1[CH2:15][CH2:14][C:13]2([C:17]3[CH:18]=[C:19]([NH:23][S:25]([CH3:24])(=[O:27])=[O:26])[CH:20]=[CH:21][CH:22]=3)[CH2:16][CH:9]1[CH2:10][CH2:11][CH2:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 962WaterHCID 31297Methanesulfonyl chlorideHCID 220645843-(2-Benzyl-2-aza-bicyclo[3.3.1]non-5-yl)-phenylamine

Product 1

HCID 22064582N-[3-(2-Benzyl-2-aza-bicyclo[3.3.1]non-5-yl)-phenyl]-methanesulfonamideYield 101%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 1140TolueneSolvent

Procedure

3-(2-Benzyl-2-aza-bicyclo[3.3.1]non-5-yl)-phenylamine (3.37 g, 9.24 mmol) in pyridine (30 ml) at 0° C. was charged with methanesulfonylchloride 1.3 ml, 16.5 mmol) dropwise, causing a color change from yellow to bright orange. The reaction was warmed to room temperature and judged complete by TLC after 3 h. The mixture was diluted with toluene and stripped twice. Following a water quench (20 ml), the product was extracted with EtOAc (4×30 ml), washed with saturated aqueous NaHCO3 solution (6×30 ml) and with saturated aqueous NaCl solution (3×30 ml), dried over Na2SO4, filtered and concentrated to a crude orange liquid. Flash chromatography on silica gel eluting with 2 to 5% MeOH/CH2Cl2 provided the title compound as orange oil (3.59 g, 85%). (TLC 5% MeOH/CH2Cl2 Rf 0.24); 1H NMR (400 MHz, CDCl3) δ 7.37–7.19 (m, 7H), 7.11 (br d, J=7.9 Hz, 1H), 7.05 (ddd, J=7.9, 2.1, 0.8 Hz, 1H), 3.73 (AB q, ΔAB 59.9, J=13.3 Hz, 2H), 3.71 (m, 1H), 3.09 (br, s, 1H), 3.04 (m, 1H), 2.94 (s, 3H), 2.80 (m, 1H), 2.18 (m, 2H), 2.07–1.95 (m, 4H), 1.82 (br d, J=12.0 Hz, 1H), 1.72 (m, 1H), 1.57 (m, 1H), 1.17 (m, 1H). 13C 154.2, 137.1, 132.3, 129.5, 129.4, 129.1, 128.6, 128.4, 127.1, 122.0, 118.3, 117.9, 60.1, 52.3, 49.4, 39.3, 38.9, 38.7, 37.4, 35.8, 24.9, 23.0; APCI MS m/z 385.1 (M+1)+.

Workup

  1. customquench (20 ml)
  2. extractionthe product was extracted with EtOAc (4×30 ml)
  3. washwashed with saturated aqueous NaHCO3 solution (6×30 ml) and with saturated aqueous NaCl solution (3×30 ml)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to a crude orange liquid

Sources & evidence

ORD record
ord-9dbddcb291224d3f942140d263a7cca7
Source dataset
uspto-grants-2006_06
Patent number
US07056930B2

Reaction notes

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