4-Bromo-1-chloro-2-(4-ethoxy-benzyl)-benzene → 1687737-72-9

HRID 1055497Notes

Reaction equation

HRID 1055497 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH3:18])=[CH:12][CH:11]=2)[CH:3]=1.C([Li])CCC.[CH3:24][Si:25]([CH3:51])([CH3:50])[O:26][C@@H:27]1[C@@H:32]([O:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C@H:31]([O:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[C@@H:30]([CH2:43][O:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[O:29][C:28]1=[O:49]>O1CCCC1>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C@@:28]2([OH:49])[C@H:27]([O:26][Si:25]([CH3:51])([CH3:50])[CH3:24])[C@@H:32]([O:33][Si:34]([CH3:35])([CH3:36])[CH3:37])[C@H:31]([O:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[C@@H:30]([CH2:43][O:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[O:29]2)=[CH:3][C:4]=1[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH3:18])=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 99964494-Bromo-1-chloro-2-(4-ethoxy-benzyl)-benzeneHCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 178418339Butyllithium

Product 1

HCID 1317363781687737-72-9Yield 106.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-bromo-1-chloro-2-(4-ethoxyphenyl)methyl-benzene (30 g, 92.1 mmol, bought from Shanghai Kinsey pharmaceutical company) in anhydrous tetrahydrofuran (250 mL) was added n-butyllithium (40.3 mL, 96.7 mmol, 2.4 M in n-hexane) dropwise at −78° C. The mixture was stirred at −78° C. for 40 min and a solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-(trimethylsilyloxymethyl) tetrahydropyran-2-one 1b (47.3 g, 101.3 mmol) in anhydrous tetrahydrofuran (50 mL) was added dropwise. After the addition, the mixture was further stirred at −78° C. for 5 hours and then quenched with 100 mL of saturated aqueous ammonium chloride. The mixture was allowed to warm up to room temperature and concentrated in vacuo. To the residue was added 150 mL of water. The resulting mixture was extracted with ethyl acetate (150 mL×3). The combined organic layers were washed with saturated aqueous sodium chloride (200 mL), dried over anhydrous sodium sulfate and concentrated in vacuo to give the title compound 1c as pale yellow oil (69.7 g, 100%). This crude product was used in next step without further purification.

Workup

  1. additionAfter the addition
  2. stirringthe mixture was further stirred at −78° C. for 5 hours
  3. customquenched with 100 mL of saturated aqueous ammonium chloride
  4. temperatureto warm up to room temperature
  5. concentrationconcentrated in vacuo
  6. additionTo the residue was added 150 mL of water
  7. extractionThe resulting mixture was extracted with ethyl acetate (150 mL×3)
  8. washThe combined organic layers were washed with saturated aqueous sodium chloride (200 mL)
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cbfa883b3064494194e9ff39fb43c64f
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

Loading…