2-Bromomethyl-1,3-dichloro-5-benzyloxy-benzene → HCID 67355242, compound

HRID 1670829Notes

Reaction equation

HRID 1670829 reaction equation
[C:1]([Si:5]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[O:6][CH:7]1[CH2:12][CH2:11][N:10]([CH:13]2[CH2:17][CH2:16][NH:15][C:14]2=[O:18])[CH2:9][CH2:8]1)([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[CH2:36]([O:43][C:44]1[CH:45]=[C:46]([Cl:53])[C:47]([CH2:51]Br)=[C:48]([Cl:50])[CH:49]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C1COCC1>[CH2:36]([O:43][C:44]1[CH:45]=[C:46]([Cl:53])[C:47]([CH2:51][N:15]2[CH2:16][CH2:17][CH:13]([N:10]3[CH2:9][CH2:8][CH:7]([O:6][Si:5]([C:1]([CH3:4])([CH3:2])[CH3:3])([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH2:12][CH2:11]3)[C:14]2=[O:18])=[C:48]([Cl:50])[CH:49]=1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

5

Reactant 3

HCID 592994282-Bromomethyl-1,3-dichloro-5-benzyloxy-benzeneHCID 67354107HCID 67354107, compoundHCID 178418339Butyllithium2×

Product 1

HCID 67355242HCID 67355242, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Treat a −78° C. solution of 3-[4-(tert-butyl-diphenyl-silanyloxy)-piperidin-1-yl]-pyrrolidin-2-one (0.25 g, 0.59 mmol) in THF (6 mL) with a 1.6 M n-butyl lithium in hexanes (0.37 mL, 0.59 mmol) and stir at −78° C. for 10 minutes under N2. Treat the reaction with 5-benzyloxy-2-bromomethyl-1,3-dichloro-benzene (0.204 g, 0.59 mmol), warm to room temperature, and stir for 16 hours under N2. Re-cool the reaction to −78° C., treat with 1.6 M n-butyl lithium in hexanes (0.37 mL, 0.59 mmol), warm to room temperature, and stir for 2 hours. Quench the reaction with water and extract with ethyl acetate. Dry the organic layer (Na2SO4), remove the solvent in vacuo to afford crude product, and purify with a 50 to 100% ethyl acetate in hexanes gradient to afford 0.263 g (65%) of the titled product. Rf=0.18 (3/1 ethyl acetate/hexanes). ES MS (m/z): 687 (M+).

Workup

  1. additionTreat
  2. temperaturewarm to room temperature
  3. stirringstir for 16 hours under N2
  4. customRe-cool the reaction to −78° C.
  5. temperaturewarm to room temperature
  6. stirringstir for 2 hours
  7. customQuench
  8. customthe reaction with water
  9. extractionextract with ethyl acetate
  10. dry with materialDry the organic layer (Na2SO4)
  11. customremove the solvent in vacuo
  12. customto afford crude product
  13. custompurify with a 50 to 100% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-fca6150f8b514d77a00677a8633c0ea9
Source dataset
uspto-grants-2011_08
Patent number
US07994176B2

Reaction notes

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