Boron tribromide → HCID 24994651, compound

HRID 423530Notes

Reaction equation

HRID 423530 reaction equation
C[O:2][CH2:3][CH2:4][S:5]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:19]=[CH:18][C:17]([O:20][CH2:21][CH:22]3[CH2:27][CH2:26][N:25]([C:28]([O:30][CH:31]([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]3)=[CH:16][CH:15]=2)=[CH:10][CH:9]=1)(=[O:7])=[O:6].B(Br)(Br)Br.C([O-])(O)=O.[Na+]>C(Cl)Cl>[OH:2][CH2:3][CH2:4][S:5]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:19]=[CH:18][C:17]([O:20][CH2:21][CH:22]3[CH2:23][CH2:24][N:25]([C:28]([O:30][CH:31]([CH3:33])[CH3:32])=[O:29])[CH2:26][CH2:27]3)=[CH:16][CH:15]=2)=[CH:10][CH:9]=1)(=[O:6])=[O:7]

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 24994650HCID 24994650, compound

Product 1

HCID 24994651HCID 24994651, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
10 °C

Procedure

A solution of 1-methylethyl 4-({[6-(4-{[2-(methoxy)ethyl]sulfonyl}phenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate (Example 81, 0.13 g, 0.27 mmol) in CH2Cl2 (10 mL) was treated with BBr3 (1.0M in CH2Cl2, 1.64 mL, 1.64 mmol) at −78° C. The reaction mixture was allowed to warm up to 10° C., and poured onto ice and aqueous NaHCO3. The mixture was extracted with EtOAc. The organic extracts were combined and washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a brown solid. The crude product was purified by chromatography on a silica gel column eluted with 2:4:0.1 EtOAc/CH2Cl2/MeOH to give 66 mg (53%) of the title compound as an off-white solid. 1H NMR (400 MHz, CD3OD): δ 8.36 (d, 1H, J=2.9 Hz), 8.17 (d, 2H, J=8.5 Hz), 8.00 (d, 2H, J=8.3 Hz), 7.92 (d, 1H, J=8.8 Hz), 7.49 (dd, 1H, Ja=8.8 Hz, Jb=2.9 Hz), 4.90-4.80 (m, 1H), 4.25-4.10 (m, 2H), 3.99 (d, 2H, J=6.1 Hz), 3.88 (t, 2H, J=6.2 Hz), 3.42 (t, 2H, J=6.2 Hz), 2.95-2.75 (m, 2H), 2.15-2.00 (m, 1H), 1.95-1.80 (m, 2H), 1.35-1.20 (m, 8H); LRMS (ESI), m/z 463 (M+H).

Workup

  1. extractionThe mixture was extracted with EtOAc
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. customto give the crude product as a brown solid
  7. customThe crude product was purified by chromatography on a silica gel column
  8. washeluted with 2:4:0.1 EtOAc/CH2Cl2/MeOH

Sources & evidence

ORD record
ord-fb7b07a86fc94e0084ab863e4989aecf
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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