2-(Bromomethyl)-1,3-dichloro-5-methoxybenzene → 1-[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexyl]-3-(2,6-dichloro-4-methoxy-benzyl)-pyrrolidin-2-one

HRID 2235302Notes

Reaction equation

HRID 2235302 reaction equation
[C:1]([Si:5]([CH3:20])([CH3:19])[O:6][C@@H:7]1[CH2:12][CH2:11][C@H:10]([N:13]2[CH2:17][CH2:16][CH2:15][C:14]2=[O:18])[CH2:9][CH2:8]1)([CH3:4])([CH3:3])[CH3:2].Br[CH2:22][C:23]1[C:28]([Cl:29])=[CH:27][C:26]([O:30][CH3:31])=[CH:25][C:24]=1[Cl:32]>>[C:1]([Si:5]([CH3:20])([CH3:19])[O:6][CH:7]1[CH2:8][CH2:9][CH:10]([N:13]2[CH2:17][CH2:16][CH:15]([CH2:22][C:23]3[C:24]([Cl:32])=[CH:25][C:26]([O:30][CH3:31])=[CH:27][C:28]=3[Cl:29])[C:14]2=[O:18])[CH2:11][CH2:12]1)([CH3:4])([CH3:3])[CH3:2]

Participants

3

Reactant 2

HCID 592994792-(Bromomethyl)-1,3-dichloro-5-methoxybenzeneHCID 178455336HCID 178455336, compound

Product 1

HCID 684705141-[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexyl]-3-(2,6-dichloro-4-methoxy-benzyl)-pyrrolidin-2-oneYield 49%

Procedure

Using the procedure to synthesize Example 202 and using the reagents of cis-1-[4-(tert-butyl-dimethyl-silanoxy)-cyclohexyl]-pyrrolidin-2-one (Preparation 17) and 2-Bromomethyl-1,3-dichloro-5-methoxy-benzene (Preparation 62). Warm reaction to room temperature, quench with NH4Cl (sat), dilute with diethyl ether, wash with brine, dry over sodium sulfate, filter and evaporate to an oil. Chromatography (silica, 100% hexanes to 75:25 hexanes/EtoAc) yields 1-[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexyl]-3-(2,6-dichloro-4-methoxy-benzyl)-pyrrolidin-2-one in 49% yield. The silylether is dissolved in THF, treated with 10.0 equivalents of HCl (conc) and allowed to stir at room temperature for 3 h, quench reaction with water, dilute with EtOAc, adjust pH to 7.0, separate, dry over sodium sulfate, filter and evaporate provides the titled compound in 84% yield: Mass spectrum (API-ES positive) m/z=372 (M+H).

Workup

  1. customto synthesize Example 202
  2. temperatureWarm
  3. customreaction to room temperature
  4. customquench with NH4Cl (sat)
  5. additiondilute with diethyl ether
  6. washwash with brine
  7. dry with materialdry over sodium sulfate
  8. filtrationfilter
  9. customevaporate to an oil

Sources & evidence

ORD record
ord-7725e73ccc5c48c4a97c12fa2697e6b3
Source dataset
uspto-grants-2010_05
Patent number
US07713979B2

Reaction notes

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