3-Bromophenol → HCID 60142342, compound

HRID 2404599Notes

Reaction equation

HRID 2404599 reaction equation
[Li]C(C)(C)C.Br[C:7]1[CH:8]=[C:9]([OH:13])[CH:10]=[CH:11][CH:12]=1.[CH3:14][C@H:15]1[C:20](=[O:21])[C@H:19]([CH2:22][N:23]([CH3:32])[CH2:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@@H:18]2[CH2:33][C@H:16]1[C:17]2([CH3:35])[CH3:34]>C1COCC1>[OH:13][C:9]1[CH:8]=[C:7]([C@@:20]2([OH:21])[C@H:19]([CH2:22][N:23]([CH3:32])[CH2:24][CH2:25][C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[C@@H:18]3[CH2:33][C@@H:16]([C:17]3([CH3:34])[CH3:35])[C@H:15]2[CH3:14])[CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 115633-BromophenolHCID 60150785HCID 60150785, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 60142342HCID 60142342, compoundYield 6.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Add a solution of t-BuLi (20 mL, 26.0 mmol) via syringe to a solution of 3-bromo-phenol (2.06 g, 12 mmol) in THF (20 mL) at −78° C. under N2. After being stirred at −78° C. for 1 hour, add a solution of (1R,2R,4S,5S)-2,6,6-trimethyl-4-((methyl(phenethyl)amino)methyl)bicyclo[3.1.1]heptan-3-one (2.99 g, 10 mmol) in THF (2 mL) to the reaction mixture and stir the reaction mixture at −78° C. for additional 2 hours. Quench the reaction with saturated NH4Cl solution (30 mL). Extract the aqueous mixture with EtOAc (60 mL×3). The combined organic layers are washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated under vacuum. Purify the residue by Preparative HPLC to give (1R,2R,3S,4S,5S)-3-(3-hydroxyphenyl)-2,6,6-trimethyl-4-((methyl(phenethyl)amino)methyl)bicyclo[3.1.1]heptan-3-ol as pale yellow oil (0.27 g, yield: 6.9%), MS (m/z): 394 (M+1).

Workup

  1. stirringstir the reaction mixture at −78° C. for additional 2 hours
  2. customQuench
  3. customthe reaction with saturated NH4Cl solution (30 mL)
  4. extractionExtract the aqueous mixture with EtOAc (60 mL×3)
  5. washThe combined organic layers are washed with brine (30 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customPurify the residue by Preparative HPLC

Sources & evidence

ORD record
ord-95f170c3900941c89c62958d81af3b9f
Source dataset
uspto-grants-2014_08
Patent number
US08802728B2

Reaction notes

Loading…