Boron tribromide → [2-(4-Trifluoromethylphenyl)-6-hydroxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone

HRID 609823Notes

Reaction equation

HRID 609823 reaction equation
[F:1][C:2]([F:38])([F:37])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:13][C:12]3[CH:14]=[C:15]([O:18]C)[CH:16]=[CH:17][C:11]=3[C:10]=2[C:20]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][N:31]3[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]3)=[CH:24][CH:23]=2)=[O:21])=[CH:5][CH:4]=1.B(Br)(Br)Br>C(Cl)Cl.O>[F:38][C:2]([F:1])([F:37])[C:3]1[CH:4]=[CH:5][C:6]([C:9]2[S:13][C:12]3[CH:14]=[C:15]([OH:18])[CH:16]=[CH:17][C:11]=3[C:10]=2[C:20]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][N:31]3[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]3)=[CH:24][CH:23]=2)=[O:21])=[CH:7][CH:8]=1

Participants

5

Reactant 2

HCID 25134Boron tribromide2×HCID 10673987[2-(4-Trifluoromethylphenyl)-6-methoxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone

Product 1

HCID 10744646[2-(4-Trifluoromethylphenyl)-6-hydroxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanoneYield 24%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

The product of Example 19 (480 mg, 0.89 mmol) was dissolved in anhydrous CH2Cl2 (15 mL), cooled to -78° C., and treated with a 1.0 M CH2Cl2 solution of boron tribromide (0.8 mL, 0.8 mmol). The mixture was allowed to warm to room temperature, stirred overnight, and treated with additional boron tribromide (1.75 mL, 1.75 mmol) in 2 portions. After 72 h, the mixture was diluted with 75 mL of water and extracted with CH2Cl2 (2×75 mL). The organic layers were washed with 2 N sodium hydroxide and the resultant aqueous layer was acidified and extracted with CH2Cl2 (75 mL). The combined organic layers were dried (Na2SO4), concentrated, and purified via radial chromatography (2:1:0.1 hexane:ethyl acetate:MeOH, under an ammonia atmosphere) to provide 110 mg (24%) of the title product as an amorphous green solid: 1H NMR d 1.45 (m, 2H), 1.63 (m, 4H), 2.57 (m, 4H), 2.79 (t, J=4.9 Hz, 2H), 4.08 (t, J=4.9 Hz, 2H), 6.59 (d, J=8.6 Hz, 2H), 6.77 (d, J=8.7 Hz, 1H), 7.15 (s, 1H), 7.33 (d, J=8.7 Hz, 1H), 7.42 (s, 4H), 7.64 (d, J=8.6 Hz, 2H), 8.18 (b, 1H); HRMS (FD+) m/e calc'd. for C29H27F3NO3S (MH+): 526.1664, found: 526.1669; Anal. calc'd for C29H26F3NO3S.H2O: C, 64.07; H, 5.20; N, 2.57. Found: C, 63.67; H, 5.12; N, 2.89.

Workup

  1. temperatureto warm to room temperature
  2. waitAfter 72 h
  3. extractionextracted with CH2Cl2 (2×75 mL)
  4. washThe organic layers were washed with 2 N sodium hydroxide
  5. extractionextracted with CH2Cl2 (75 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. concentrationconcentrated
  8. custompurified via radial chromatography (2:1:0.1 hexane

Sources & evidence

ORD record
ord-e9efe6884c424c7eacd1aae4b1d6d56d
Source dataset
uspto-grants-1999_12
Patent number
US05998442

Reaction notes

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