Boron tribromide → HCID 54766104, compound

HRID 534249Notes

Reaction equation

HRID 534249 reaction equation
B(Br)(Br)Br.C[O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[CH:12]([C:16]1[CH:29]=[CH:28][C:19]([O:20][CH2:21][CH2:22][N:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:18][CH:17]=1)[CH:11]([C:30]1[CH:35]=[CH:34][C:33]([O:36]C)=[CH:32][CH:31]=1)[CH2:10]2>ClCCl>[OH:36][C:33]1[CH:32]=[CH:31][C:30]([CH:11]2[CH2:10][C:9]3[C:13](=[CH:14][CH:15]=[C:7]([OH:6])[CH:8]=3)[CH:12]2[C:16]2[CH:29]=[CH:28][C:19]([O:20][CH2:21][CH2:22][N:23]3[CH2:24][CH2:25][CH2:26][CH2:27]3)=[CH:18][CH:17]=2)=[CH:35][CH:34]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 68001233HCID 68001233, compound

Product 1

HCID 54766104HCID 54766104, compoundYield 60.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Boron tribromide (0.16 mL, 1M in CH2Cl2, 0.16 mmol) was added dropwise to a solution of 1-(2-(4-(5-methoxy-2-(4-methoxyphenyl)-2,3-dihydro-1H-inden-1-yl)phenoxy)ethyl)pyrrolidine (18 mg, 0.04 mmol) and dichloromethane (2.5 mL) at 0° C. under N2. After 20 min, the reaction was allowed to warm to rt. After an additional hour, the reaction was quenched with methanol (0.4 mL), poured into saturated aqueous NaHCO3 (40 mL), and extracted with 5% methanol in dichloromethane (50 mL×2). The organic extracts were dried (MgSO4), filtered, concentrated, and purified by reverse-phase HPLC (CH3CN, H2O, TFA) to give 10 mg of 2-(4-hydroxyphenyl)-1-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2,3-dihydro-1H-inden-5-ol as the trifluoroacetate salt. 1H NMR (400 MHz, DMSO-d6): δ 9.61 (br, 1H), 9.22 (br, 1H), 8.99 (br, 1H), 6.81-6.75 (m, 2H), 6.72-6.62 (m, 4H), 6.60-6.52 (m, 3H), 6.44 (d, 2H), 4.45 (d, 1H), 4.15 (t, 2H), 3.91-3.79 (m, 1H), 3.62-3.48 (m, 4H), 3.23-2.98 (m, 4H), 2.08-1.80 (m, 4H); LCMS: 416.6 (M+H)+.

Workup

  1. waitAfter an additional hour
  2. customthe reaction was quenched with methanol (0.4 mL)
  3. additionpoured into saturated aqueous NaHCO3 (40 mL)
  4. extractionextracted with 5% methanol in dichloromethane (50 mL×2)
  5. dry with materialThe organic extracts were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by reverse-phase HPLC (CH3CN, H2O, TFA)

Sources & evidence

ORD record
ord-3f4ac238ef034aba8c40c9b049a923a5
Source dataset
uspto-grants-2014_10
Patent number
US08853423B2

Reaction notes

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