Sodium Thiosulfate Pentahydrate → HCID 10573186, compound

HRID 1421663Notes

Reaction equation

HRID 1421663 reaction equation
[C:1]1([CH2:7][CH2:8][C@:9]([O:16][CH2:17][O:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:21][CH:20]=2)([CH2:13][CH2:14][CH3:15])[CH2:10][CH2:11][OH:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br-].[K+].C(=O)(O)[O-].[Na+].Cl[O-].[Na+].O.O.O.O.O.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)Cl.O>[C:1]1([CH2:7][CH2:8][C@:9]([O:16][CH2:17][O:18][C:19]2[CH:20]=[CH:21][C:22]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:23][CH:24]=2)([CH2:13][CH2:14][CH3:15])[CH2:10][CH:11]=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 5

HCID 61475Sodium Thiosulfate PentahydrateHCID 253877Potassium BromideHCID 516892Sodium BicarbonateHCID 15378772HCID 15378772, compoundHCID 23665760Sodium Hypochlorite

Product 1

HCID 10573186HCID 10573186, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a mixture of crude (R)-3-(2-phenylethyl)-3-[(4-phenylphenoxy)methoxy]hexanol (XI, EXAMPLE 8, 91.1 wt %, 15.40 g, 34.68 mmol) in methylene chloride (47 ml) at 0° is added a solution of potassium bromide (0.4057 35 g, 3.409 mmol, 0.098 equiv) and sodium bicarbonate (1.557 g, 18.53 mmol, 0.53 equiv) in water (20.5 ml) followed by 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy, free radical (0.3060 g, 1.776 mmol, 0.051 equiv). Aqueous sodium hypochlorite (13.4 wt %/vol, 26.6 ml, 47.88 mmol, 1.38 equiv) is then added by syringe pump over 1 hr while maintaining 1-5°. A solution of sodium thiosulfate pentahydrate (0.5182 g, 2.088 mmol, 0.0602 equiv) in water (14 ml) is then added. The phases are separated at 0° and the aqueous phase is washed with 2×50 ml methylene chloride. The organic phases are immediately filtered through magnesol (50.25 g) and rinsed through with methylene chloride (400 ml). The extracts are concentrated to an oil (30 g) and hexane (500 ml) is added. The mixture is concentrated to 250 g net weight and hexane (100 ml) added. The mixture is concentrated to 186 g net weight and pentane (300 ml) added. The resultant slurry is cooled to -50° and the desired product collected by vacuum filtration, washed with -50° pentane (100 ml) and dried to give a solid, analytically pure to give the title compound, mp=47.0-48.5°; TLC Rf=0.41 (ethyl acetate/hexane, 10/90); HPLC rt=10.95 min; NMR (CDCl3) 9.79, 7.53, 7.40, 7.26, 7.20-7.08, 5.40, 2.67, 2.65-2.56, 1.99, 1.76, 1.38, 0.93 δ; CMR (CDCl3) 201.83, 156.90, 141.69, 140.68, 134.82, 128.72, 128.47, 128.29, 128.24, 126.77, 125.99, 116.03, 87.19, 80.36, 50.14, 39.21, 39.14, 29.74, 16.86, 14.45 δ; MS (CI, NH3) m/z (relative intensity) 420 (3.5), 220 (100); [α]25D =14 (C=1.0, methylene chloride).

Workup

  1. temperaturewhile maintaining 1-5°
  2. customThe phases are separated at 0°
  3. washthe aqueous phase is washed with 2×50 ml methylene chloride
  4. filtrationThe organic phases are immediately filtered through magnesol (50.25 g)
  5. washrinsed through with methylene chloride (400 ml)
  6. concentrationThe extracts are concentrated to an oil (30 g) and hexane (500 ml)
  7. additionis added
  8. concentrationThe mixture is concentrated to 250 g net weight and hexane (100 ml)
  9. additionadded
  10. concentrationThe mixture is concentrated to 186 g net weight and pentane (300 ml)
  11. additionadded
  12. temperatureThe resultant slurry is cooled to -50°
  13. filtrationthe desired product collected by vacuum filtration
  14. washwashed with -50° pentane (100 ml)
  15. customdried
  16. customto give a solid

Sources & evidence

ORD record
ord-baa8d2624dec4c3aa184429620a3aefd
Source dataset
uspto-grants-2000_06
Patent number
US06077963

Reaction notes

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