N-(2-(p-bromophenoxy)ethyl)pyrrolidine → HCID 21862737, compound

HRID 1282244Notes

Reaction equation

HRID 1282244 reaction equation
Br[C:2]1[CH:15]=[CH:14][C:5]([O:6][CH2:7][CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.C([Li])CCC.[CH3:21][O:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][C:32]=1[O:33][CH3:34])[C:29](=O)[CH2:28][CH2:27][CH2:26]2>CCOCC.C1COCC1>[CH3:34][O:33][C:32]1[CH:31]=[C:30]2[C:25](=[CH:24][C:23]=1[O:22][CH3:21])[C:26]([C:2]1[CH:15]=[CH:14][C:5]([O:6][CH2:7][CH2:8][N:9]3[CH2:13][CH2:12][CH2:11][CH2:10]3)=[CH:4][CH:3]=1)=[CH:27][CH2:28][CH2:29]2

Participants

6

Reactant 3

HCID 70657N-(2-(p-bromophenoxy)ethyl)pyrrolidineHCID 2668163,4-Dihydro-6,7-dimethoxy-1(2H)-naphthalenoneHCID 178418339Butyllithium

Product 1

HCID 21862737HCID 21862737, compoundYield 36.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 6.75 g (0.025 moles) of 1-(2-(4-bromophenoxy)ethyl)pyrrolidine in 250 ml of ether was cooled to −78° C. under N2. Several ml of THF were added to maintain a clear solution. 16.7 ml of 1.6 M n-butyllithium was added dropwise keeping the temperature below −70° C. After stirring at −78° C. for 1 hour, a solution of 5 g (0.024 moles) of 6,7-dimethoxy-1-tetralone in 25 ml of THF was added dropwise during 1 hour keeping the temperature below −70° C. After stirring for 2.5 hours at −78° C., the reaction was quenched by addition of 100 ml of 2N HCl. The reaction was allowed to warm to room temperature and the pH was adjusted to 7 by addition of 5N NaOH. The Et2O layer was separated and the aqueous layer was extracted 2 times with EtOAc. The combined Et2O/EtOAc layers were dried over Na2SO4 and evaporated to give 9 g of crude product, which was purified on 400 g of silica gel eluting with 95/5 CH2Cl2/MeOH to remove starting tetralone then with 85/15 CH2Cl2/MeOH to give 3.3 g of product.

Workup

  1. temperatureto maintain a clear solution
  2. customthe temperature below −70° C
  3. customthe temperature below −70° C
  4. stirringAfter stirring for 2.5 hours at −78° C.
  5. customthe reaction was quenched by addition of 100 ml of 2N HCl
  6. temperatureto warm to room temperature
  7. additionthe pH was adjusted to 7 by addition of 5N NaOH
  8. customThe Et2O layer was separated
  9. extractionthe aqueous layer was extracted 2 times with EtOAc
  10. dry with materialThe combined Et2O/EtOAc layers were dried over Na2SO4
  11. customevaporated
  12. customto give 9 g of crude product, which
  13. customwas purified on 400 g of silica gel eluting with 95/5 CH2Cl2/MeOH
  14. customto remove

Sources & evidence

ORD record
ord-e4b639fe752c4d39880473e380fd5636
Source dataset
uspto-grants-2002_09
Patent number
US06455572B1

Reaction notes

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