Ethanol → HCID 11266483, compound

HRID 2115198Notes

Reaction equation

HRID 2115198 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]([C:9]([C:23]2[CH:27]=[CH:26][S:25][CH:24]=2)=[C:10]2[CH2:16][CH:15]3[N:17](CC=C(C)C)[CH:12]([CH2:13][CH2:14]3)[CH2:11]2)[CH:6]=[CH:7][CH:8]=1.B(Br)(Br)Br.C([O-])(O)=O.[Na+].C(O)C>ClCCl>[CH:12]12[NH:17][CH:15]([CH2:14][CH2:13]1)[CH2:16][C:10](=[C:9]([C:23]1[CH:27]=[CH:26][S:25][CH:24]=1)[C:5]1[CH:4]=[C:3]([OH:2])[CH:8]=[CH:7][CH:6]=1)[CH2:11]2

Participants

6

Reactant 4

HCID 702EthanolHCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 59813157HCID 59813157, compound

Product 1

HCID 11266483HCID 11266483, compoundYield 24.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To 400 mg (1.05 mmol) of 3-[(3-methoxy-phenyl)-thiophen-3-yl-methylene]-8-(3-methyl-but-2-enyl)-8-aza-bicyclo[3.2.1]octane in 12 mL of dichloromethane at −78° C. was added 8.43 mL ([1M] in DCM) of boron tribromide drop wise. The reaction solution was slowly warmed to room temperature over 1 hr and allowed to stir 3 hr at room temperature. After 3 hr, to the reaction solution was added 20 mL of a saturated solution of NaHCO3, and 20 mL of 20% ethanol in DCM. The aqueous phase was removed. The organic phase was washed with 20 mL of brine, dried over MgSO4, and concentrated. The concentrated sample was purified by reverse phase chromatography (20×100 mm J'sphere H-80 YMC column using a gradient of 0.1% TFA/water to 5% water/0.1% TFA/acetonitrile). The eluent corresponding to 3-[(8-Aza-bicyclo[3.2.1]oct-3-ylidene)-thiophen-3-yl-methyl]-phenol (earlier eluent) was evaporated to yield 76 mg of the title compound as a white solid; MS m/z (MH+) 298; 1H NMR 300 MHz (MeOD-d4) δ 7.34-7.36 (dd,1H), 7.13-7.18 (m, 2H), 6.86-6.88 (dd, 1H), 6.58-6.70 (m, 3H), 3.99-4.04 (m, 2H), 2.48-2.80 (m, 4H), 1.90-2.06 (m, 4H).

Workup

  1. waitAfter 3 hr
  2. customThe aqueous phase was removed
  3. washThe organic phase was washed with 20 mL of brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe concentrated sample was purified by reverse phase chromatography (20×100 mm J'sphere H-80 YMC column
  7. customThe eluent corresponding to 3-[(8-Aza-bicyclo[3.2.1]oct-3-ylidene)-thiophen-3-yl-methyl]-phenol (earlier eluent) was evaporated

Sources & evidence

ORD record
ord-eb53ce1dbbe7496cbf1329cbab1bb2fb
Source dataset
uspto-grants-2008_10
Patent number
US07435822B2

Reaction notes

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