4-Toluenesulfonyl chloride → HCID 89622582, compound

HRID 400354Notes

Reaction equation

HRID 400354 reaction equation
[OH:1][CH2:2][CH2:3][C:4]([P:7](=[O:14])([O:11][CH2:12][CH3:13])[O:8][CH2:9][CH3:10])([F:6])[F:5].C(N(CC)CC)C.[S:22](Cl)([C:25]1[CH:31]=[CH:30][C:28]([CH3:29])=[CH:27][CH:26]=1)(=[O:24])=[O:23]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[S:22]([O:1][CH2:2][CH2:3][C:4]([P:7](=[O:14])([O:11][CH2:12][CH3:13])[O:8][CH2:9][CH3:10])([F:6])[F:5])([C:25]1[CH:31]=[CH:30][C:28]([CH3:29])=[CH:27][CH:26]=1)(=[O:24])=[O:23]

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chloride2×HCID 8471TriethylamineHCID 89622261Diethyl (1,1-difluoro-3-hydroxypropyl)phosphonate

Product 1

HCID 89622582HCID 89622582, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Diethyl 3-hydroxy-1,1-difluoro-propylphosphonate [1225194-19-3](4.4 g, 0.019 mol) was dissolved in CH2Cl2 (20 mL) and triethylamine (7.7 g) and treated with TsCl (5.4 g, 0.029 mol) followed by DMAP (0.23 g, 0.0019 mol) at rt for 2 h. After 2 h, an additional portion of TsCl (0.6 g) was added. After 30 m, the reaction mixture was partitioned between water and CH2Cl2. The organic layer was filtered and concentrated in vacuo. The residue was dissolved in 1:1 hexanes:CH2Cl2 (100 mL) and applied to 85 g flash silica gel (topped with Na2SO4 and equilibrated with hexanes). The column was eluted with hexanes-ethyl acetate. Intermediate 23 weighed 6.3 g (94%). 1H NMR (CDCl3) 7.2-7.8 (AB, 4H); 3.9-4.4 (m, 6H); 2.0-3.0 (m, 5H), 1.4 (t, 6H).

Workup

  1. customAfter 30 m, the reaction mixture was partitioned between water and CH2Cl2
  2. filtrationThe organic layer was filtered
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in 1:1 hexanes
  5. washThe column was eluted with hexanes-ethyl acetate

Sources & evidence

ORD record
ord-68d3820112a24757b483548930ce0911
Source dataset
uspto-grants-2014_06
Patent number
US08741875B2

Reaction notes

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