3-Butyn-1-OL → N-(6,6-dimethyl bicyclo[3.1.1]heptan-2-yl)-4-(4-hydroxybut-1-ynyl)benzenesulphonamide

HRID 717643

Reaction equation

HRID 717643 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][CH:12]2[CH2:17][CH2:16][CH:15]3[CH2:18][CH:13]2[C:14]3([CH3:20])[CH3:19])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH2:21]([OH:25])[CH2:22][C:23]#[CH:24]>CN(C=O)C.CCN(C(C)C)C(C)C>[CH3:19][C:14]1([CH3:20])[CH:13]2[CH2:18][CH:15]1[CH2:16][CH2:17][CH:12]2[NH:11][S:8]([C:5]1[CH:6]=[CH:7][C:2]([C:24]#[C:23][CH2:22][CH2:21][OH:25])=[CH:3][CH:4]=1)(=[O:10])=[O:9]

Participants

5

Reactant 2

HCID 135663-Butyn-1-OLHCID 666149414-Bromo-N-(6,6-dimethylbicyclo[3.1.1]heptan-2-yl)benzene sulfonamide

Product 1

HCID 66614933N-(6,6-dimethyl bicyclo[3.1.1]heptan-2-yl)-4-(4-hydroxybut-1-ynyl)benzenesulphonamideYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 81531DiisopropylethylamineSolvent

Procedure

A solution of the product of Step A (0.37 g, 0.5 mmol) and but-3-yn-1-ol (0.12 ml, excess) in a mixture of DMF (5 ml) and DIPEA (0.5 ml) was degassed with N2 and Cl2Pd(PPh3)2 (0.07 g) was added, followed by catalytic amount of CuI and the mixture was stirred for 16 h at room temperature. The reaction was quenched with saturated NH4Cl solution and diluted with H2O followed by the extraction with EtOAc (100 ml). The organic layer was separated, dried over MgSO4, filtered and the filtrate was evaporated to dryness and the residue was purified by FCC (SiO2, hexane/EtOAc) to give the product (0.11 g, 60%), as creamy paste. 1H-NMR (CDCl3) 7.66 (d, 2H, J=8.43 Hz); 7.51 (d, 2H, J=8.43 Hz); 3.81 (b, 2H); 3.01-2.86 (m, 2H); 2.71-2.67 (m, 4H); 2.50-2.10 (m, 2H); 1.94-1.82 (m, 5H); 1.52-1.48 (m, 1H); 1.18 (s, 3H); 1.02 (s, 3H).

Workup

  1. customwas degassed with N2 and Cl2Pd(PPh3)2 (0.07 g)
  2. additionwas added
  3. customThe reaction was quenched with saturated NH4Cl solution
  4. additiondiluted with H2O
  5. extractionfollowed by the extraction with EtOAc (100 ml)
  6. customThe organic layer was separated
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customthe filtrate was evaporated to dryness
  10. customthe residue was purified by FCC (SiO2, hexane/EtOAc)

Sources & evidence

ORD record
ord-e5eed6baeb1442408153a3ce29416f96
Source dataset
uspto-grants-2015_11
Patent number
US09193716B2

Linked notes

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