Hydrochloric Acid → Vilanterol

HRID 901630Notes

Reaction equation

HRID 901630 reaction equation
Cl.[Cl:2][C:3]1[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:4]=1[CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][NH:16][CH2:17][C@@H:18]([C:20]1[CH:21]=[CH:22][C:23]2[O:28]C(C)(C)[O:26][CH2:25][C:24]=2[CH:31]=1)[OH:19].C(=O)(O)[O-].[Na+].ClCCl>C(O)C>[Cl:2][C:3]1[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:4]=1[CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][NH:16][CH2:17][C@@H:18]([C:20]1[CH:21]=[CH:22][C:23]([OH:28])=[C:24]([CH2:25][OH:26])[CH:31]=1)[OH:19]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 46834265(1R)-2-(6-(2-((2,6-dichlorophenyl)methoxy)ethoxy)hexylamino)-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)ethanol

Product 1

HCID 10184665VilanterolYield 73.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1N HCl (295 mL) was added to a solution of (R)-2-{6-[2-(2,6-dichlorobenzyloxy)-ethoxy]-hexylamino}-1-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)-ethanol (52 g, 0.099 mol) in ethanol (312 mL), and the reaction stirred at ambient temperature for 1.5 h. Saturated sodium bicarbonate solution (500 mL) was added followed by dichloromethane (500 mL). The aqueous layer was separated and extracted with further dichloromethane (500 mL). The combined organic solutions were washed with water/brine mixture (500 mL/100 mL), then evaporated. The residue (50 g) was chromatographed on silica (800 g, Biotage) eluting with a dichloromethane/ethanol/ammonia mixture (50/8/1), to afford the title compound as an oil (35.2 g)—LC RT=4.1 min.

Workup

  1. customThe aqueous layer was separated
  2. extractionextracted with further dichloromethane (500 mL)
  3. washThe combined organic solutions were washed with water/brine mixture (500 mL/100 mL)
  4. customevaporated
  5. customThe residue (50 g) was chromatographed on silica (800 g, Biotage)
  6. washeluting with a dichloromethane/ethanol/ammonia mixture (50/8/1)

Sources & evidence

ORD record
ord-951c78745d2745d5ba4d48f651b279e0
Source dataset
uspto-grants-2008_04
Patent number
US07361787B2

Reaction notes

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