Sodium hydride → HCID 86603467, compound

HRID 2108659Notes

Reaction equation

HRID 2108659 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([OH:22])[CH:7]=[C:8]([Br:21])[C:9]=1[O:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([CH:18]([CH3:20])[CH3:19])[CH:12]=1.ClC1C=CC(S(O[CH2:34][P:35](=[O:40])([O:38][CH3:39])[O:36][CH3:37])(=O)=O)=CC=1>CN(C=O)C>[Br:3][C:4]1[CH:5]=[C:6]([CH:7]=[C:8]([Br:21])[C:9]=1[O:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([CH:18]([CH3:20])[CH3:19])[CH:12]=1)[O:22][CH2:34][P:35](=[O:40])([O:38][CH3:39])[O:36][CH3:37]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10245140HCID 10245140, compoundHCID 10250498HCID 10250498, compound

Product 1

HCID 86603467HCID 86603467, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirring mixture of DMF (20.0 mL) and NaH (0.074 g, 1.86 mmol) at 0° C. was added 3,5-dibromo-4-(3-isopropyl-4-hydroxy-phenoxy)phenol (Intermediate for the synthesis of compound 8-1, 0.75 g, 1.86 mmol) dissolved in DMF (2.0 mL). The reaction mixture was allowed to stir at rt for 1 hr and cooled to 0° C. Dimethyl 4-chloro-benzenesulfonyloxymethylphosphonate (0.11 g, 0.36 mmol) was added and the reaction mixture was stirred at rt for 16 h. The reaction was quenched with ice H2O, the pH was adjusted to 1 with 2 M HCl, and the mixture was partitioned with ethyl acetate and H2O. The organic layer was concentrated and coevaporated with acetone (2×). The residue was treated with a hexane/ethyl acetate mixture and sonicated to afford dimethyl [3,5-dibromo-4-(4-hydroxy-3-iso-propyl-phenoxy)phenoxy]methylphosphonate as a white solid precipitate (0.070 g, 34%): 1H NMR (200 MHz, DMSO-d6): δ 9.00 (s, 1H), 7.47 (s, 2H), 6.65 (m, 2H), 6.23 (m, 1H), 4.60 (d, J=10.0 Hz, 2H), 3.75 (d, J=10.0 Hz, 6H), 3.12 (m, 1H), 1.09 (d, J=6.0 Hz, 6 H); TLC conditions: Uniplate silica gel, 250 microns; Mobile phase=ethyl acetate; Rf=0.60

Workup

  1. temperaturecooled to 0° C
  2. stirringthe reaction mixture was stirred at rt for 16 h
  3. customThe reaction was quenched with ice H2O
  4. customthe mixture was partitioned with ethyl acetate and H2O
  5. concentrationThe organic layer was concentrated
  6. additionThe residue was treated with a hexane/ethyl acetate mixture
  7. customsonicated

Sources & evidence

ORD record
ord-b1d1dae10a604ac28925c69d1c39fc4c
Source dataset
uspto-grants-2009_04
Patent number
US07514419B2

Reaction notes

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