4-Bromo-1-chloro-2-(4-ethoxy-benzyl)-benzene → HCID 66884302, compound

HRID 2204041Notes

Reaction equation

HRID 2204041 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.[Li]CCCC.[C:24]([Si:28]([CH3:43])([CH3:42])[O:29][C@H:30]1[C@H:37]2[C@H:33]([O:34][C:35]([CH3:39])([CH3:38])[O:36]2)[O:32][C@H:31]1[CH:40]=[O:41])([CH3:27])([CH3:26])[CH3:25]>C1COCC1>[C:24]([Si:28]([CH3:43])([CH3:42])[O:29][C@H:30]1[C@H:37]2[C@H:33]([O:34][C:35]([CH3:38])([CH3:39])[O:36]2)[O:32][C@H:31]1[C@H:40]([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)[OH:41])([CH3:27])([CH3:26])[CH3:25]

Participants

5

Reactant 3

HCID 99964494-Bromo-1-chloro-2-(4-ethoxy-benzyl)-benzeneHCID 59431063HCID 59431063, compoundHCID 178418339Butyllithium

Product 1

HCID 66884302HCID 66884302, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-bromo-1-chloro-2-(4-ethoxy-benzyl)-benzene from step C (3.6 g, 11.1 mmol) in THF (60 ml) under N2 at −78° C. was added dropwise BuLi (2.5 M in hexanes, 4.4 ml, 11.1 mmol). After 30 minutes, aldehyde from step B (2.4 g, 64% clean, 5.1 mmol) in THF (20 ml) was added dropwise, and the reaction was stirred for 30 min at −78° C., allowed to warm to room temperature and stirred for 60 minutes, quenched with sat. aq. NH4Cl, diluted with Et2O, and washed with H2O and brine. The combined aqueous washes were back extracted with Et2O, which was washed by the same sequence. The combined organic extracts were dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by flash chromatography (120 g SiO2, 0-20% EtOAc:Hexanes, 75 minutes, 85 ml/min) to give clean (S)-[(3aS,5S,6R,6aS)-6-(tert-butyl-dimethyl-silanyloxy)-2,2-dimethyl-tetrahydro-furo[2,3-d][1,3]dioxol-5-yl]-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-methanol (0.84 g, 1.5 mmol, 30%) plus the C5 epimer (0.83 g) and some mixed fractions (0.51 g).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 60 minutes
  3. customquenched with sat. aq. NH4Cl
  4. additiondiluted with Et2O
  5. washwashed with H2O and brine
  6. extractionThe combined aqueous washes were back extracted with Et2O, which
  7. washwas washed by the same sequence
  8. dry with materialThe combined organic extracts were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum
  11. customThe residue was purified by flash chromatography (120 g SiO2, 0-20% EtOAc:Hexanes, 75 minutes, 85 ml/min)

Sources & evidence

ORD record
ord-0dd805ae569440138f02ab2225f4e603
Source dataset
uspto-grants-2016_06
Patent number
US09365602B2

Reaction notes

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