Boron tribromide → 6-(4-Methanesulfonyl-phenyl)-5-[4-(2-piperidin-1-yl-ethylamino)-phenoxy]-naphthalen-2-ol dihydrochloride

HRID 748920Notes

Reaction equation

HRID 748920 reaction equation
[ClH:1].O1CCOCC1.C(OC(=O)[N:14]([C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]2[C:39]3[C:34](=[CH:35][C:36]([O:40]C)=[CH:37][CH:38]=3)[CH:33]=[CH:32][C:31]=2[C:42]2[CH:47]=[CH:46][C:45]([S:48]([CH3:51])(=[O:50])=[O:49])=[CH:44][CH:43]=2)=[CH:25][CH:24]=1)[CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)(C)(C)C.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>ClCCl>[ClH:1].[ClH:1].[CH3:51][S:48]([C:45]1[CH:44]=[CH:43][C:42]([C:31]2[C:30]([O:29][C:26]3[CH:27]=[CH:28][C:23]([NH:14][CH2:15][CH2:16][N:17]4[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]4)=[CH:24][CH:25]=3)=[C:39]3[C:34](=[CH:33][CH:32]=2)[CH:35]=[C:36]([OH:40])[CH:37]=[CH:38]3)=[CH:47][CH:46]=1)(=[O:50])=[O:49]

Participants

6

Reactant 4

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 204431481,4-Dioxane hydrochlorideHCID 59751432{4-[2-(4-Methanesulfonyl-phenyl)-6-methoxy-naphthalen-1-yloxy]-phenyl}-(2-piperidin-1-yl-ethyl)-carbamic acid tert-butyl ester

Product 1

HCID 685170416-(4-Methanesulfonyl-phenyl)-5-[4-(2-piperidin-1-yl-ethylamino)-phenoxy]-naphthalen-2-ol dihydrochlorideYield 81.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add 4M HCl/dioxane (3 mL, 12 mmol) to a solution of the compound of Example 57 (10 mg, 0.17 mmol) in dichloromethane (3 mL) and stir the reaction for 40 minutes, then evaporate to dryness under reduced pressure. Dissolve the residue in dichloromethane (4 mL) and add boron tribromide (0.068 mL, 0.72 mmol). Stir the reaction for 3.5 hours, then add aqueous saturated sodium bicarbonate (5 mL) and allow the phases to separate. Dry the organic layer with solid magnesium sulfate and chromatograph on silica gel with dichloromethane/methanol mixtures. Evaporate the fractions containing product to dryness and redissolve in 5% methanol/dichloromethane (3 mL). Add 1M hydrogen chloride in diethyl ether (0.28 mL) then evaporate the solution under reduced pressure to give 82 mg of the title compound (77%). Mass spectrum (ion spray): m/z=517.5 (M+H).

Workup

  1. customthe reaction for 40 minutes
  2. customevaporate to dryness under reduced pressure
  3. dissolutionDissolve the residue in dichloromethane (4 mL)
  4. stirringStir
  5. customthe reaction for 3.5 hours
  6. customto separate
  7. dry with materialDry the organic layer with solid magnesium sulfate and chromatograph on silica gel with dichloromethane/methanol mixtures
  8. customEvaporate the fractions
  9. additioncontaining product to dryness
  10. dissolutionredissolve in 5% methanol/dichloromethane (3 mL)
  11. additionAdd 1M hydrogen chloride in diethyl ether (0.28 mL)
  12. customthen evaporate the solution under reduced pressure

Sources & evidence

ORD record
ord-8873455cc4b049f995a9fd44a7ea24d2
Source dataset
uspto-grants-2008_07
Patent number
US07399867B2

Reaction notes

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