Cesium carbonate → N-(4-cyanobenzyl)-N-(7-hydroxybicyclo[2.2.1]heptan-2-yl)-4-chlorobenzenesulfonamide

HRID 1011549Notes

Reaction equation

HRID 1011549 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][CH:12]2[CH2:17][CH:16]3[CH:18]([OH:19])[CH:13]2[CH2:14][CH2:15]3)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:27][C:28]1[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=1>CN(C)C=O>[C:32]([C:31]1[CH:34]=[CH:35][C:28]([CH2:27][N:11]([CH:12]2[CH2:17][CH:16]3[CH:18]([OH:19])[CH:13]2[CH2:14][CH2:15]3)[S:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)(=[O:9])=[O:10])=[CH:29][CH:30]=1)#[N:33]

Participants

5

Reactant 3

HCID 10796Cesium carbonate2×HCID 869964-(Bromomethyl)benzonitrile2×HCID 594977942-(4-Chlorophenylsulfonamido)bicyclo[2.2.1]heptan-7-ol

Product 1

HCID 59497811N-(4-cyanobenzyl)-N-(7-hydroxybicyclo[2.2.1]heptan-2-yl)-4-chlorobenzenesulfonamideYield 49.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(4-chlorophenylsulfonamido)bicyclo[2.2.1]heptan-7-ol (604 mg, 2.0 mmol), cesium carbonate (1.30 g, 4.0 mmol), and 4-(bromomethyl)benzonitrile (471 mg, 2.4 mmol) was stirred in 10 mL dimethylformamide for 1 h. The crude reaction product was treated with additional cesium carbonate (261 mg, 0.8 mmol) and 4-(bromomethyl)benzonitrile (94 mg, 0.5 mmol) to complete the reaction. The reaction was partitioned between 50 mL ethyl acetate and 50 mL 0.1 M HCl, concentrated and purified by flash chromatography on 120 g silica gel with 30 to 50% ethyl acetate in hexane to yield N-(4-cyanobenzyl)-N-(7-hydroxybicyclo[2.2.1]heptan-2-yl)-4-chlorobenzenesulfonamide (412 mg, 49%). 1H NMR (400 MHz, CDCl3) δ ppm 7.70-7.77 (2H, m), 7.59 (2H, d, J=8.56 Hz), 7.44-7.50 (4H, m), 4.81 (2H, dd, J=39.53, 17.88 Hz), 4.06 (1H, t, J=7.81 Hz), 3.84 (1H, br. s.), 1.91 (1H, br. s.), 1.75-1.82 (2 Hon), 1.43-1.66 (3H, m), 1.07-1.17 (2H, m). LC/MS R.T.=1.97 min; [M+H]+=417.15.

Workup

  1. customThe crude reaction product
  2. customthe reaction
  3. customThe reaction was partitioned between 50 mL ethyl acetate and 50 mL 0.1 M HCl
  4. concentrationconcentrated
  5. custompurified by flash chromatography on 120 g silica gel with 30 to 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-dabcec8563f34081ad9bbcab38c35720
Source dataset
uspto-grants-2011_07
Patent number
US07977362B2

Reaction notes

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