1-Bromo-4-phenylmethoxybenzene → methyl (2S)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-oxo-5-{4-[(phenylmethyl)oxy]phenyl}pentanoate

HRID 1691489Notes

Reaction equation

HRID 1691489 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:9][CH:8]=1.[O:21]=[C:22]1[N:26]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@H:25]([C:34]([O:36][CH3:37])=[O:35])[CH2:24][CH2:23]1>C1COCC1>[CH3:33][C:30]([O:29][C:27]([NH:26][C@@H:25]([CH2:24][CH2:23][C:22](=[O:21])[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:9][CH:8]=1)[C:34]([O:36][CH3:37])=[O:35])=[O:28])([CH3:31])[CH3:32]

Participants

5

Reactant 3

HCID 1388351-Bromo-4-phenylmethoxybenzeneHCID 108684851-O-tert-butyl 2-O-methyl (2S)-5-oxopyrrolidine-1,2-dicarboxylateHCID 178418339Butyllithium

Product 1

HCID 59164841methyl (2S)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-oxo-5-{4-[(phenylmethyl)oxy]phenyl}pentanoateYield 32.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-Butyl lithium 1.6M solution in hexanes (0.88 ml, 1.4 mmol) was added dropwise to a solution of commercially available 1-bromo-4-[(phenylmethyl)oxy]benzene (390 mg, 1.48 mmol) in dry THF (2 ml) at −78° C. under nitrogen atmosphere. The resulting suspension was stirred at −78° C. for 40 minutes and then it was added dropwise to a solution of 1-(1,1-dimethylethyl) 2-methyl (2S)-5-oxo-1,2-pyrrolidinedicarboxylate (D1, 300 mg, 1.23 mmol) in dry THF (2.4 ml) previously cooled to −78° C. The mixture was stirred at −78° C. for 40 minutes and at −40° C. for 1 h, then it was quenched at −40° C. with an aqueous saturated ammonium chloride solution. The mixture was diluted with water and extracted with ethyl acetate. The organic phase was then washed with brine, dried over Na2SO4, and evaporated under reduced pressure to give the crude material, which was purified by chromatography on silica gel eluting with cyclohexane/ethylacetate (95:5), thus affording the title compound as a white solid (170 mg, 32%); Rf (cyclohexane:ethyl acetate=8:2): 0.30; 1HNMR (300 MHz, CDCl3) δ (ppm): 7.95 (d, 2H), 7.50-7.33 (m, 5H), 7.03 (d, 2H), 5.20 (bs, 1H), 5.15 (s, 2H), 4.45-4.35 (m, 1H), 3.78 (s, 3H), 3.15-2.95 (m, 2H), 2.36-2.26 (m, 1H), 2.16-2.02 (m, 1H), 1.45 (s, 9H).

Workup

  1. temperaturepreviously cooled to −78° C
  2. stirringThe mixture was stirred at −78° C. for 40 minutes and at −40° C. for 1 h
  3. customit was quenched at −40° C. with an aqueous saturated ammonium chloride solution
  4. additionThe mixture was diluted with water
  5. extractionextracted with ethyl acetate
  6. washThe organic phase was then washed with brine
  7. dry with materialdried over Na2SO4
  8. customevaporated under reduced pressure
  9. customto give the crude material, which
  10. customwas purified by chromatography on silica gel eluting with cyclohexane/ethylacetate (95:5)

Sources & evidence

ORD record
ord-b8159dfdd6ed4f4b8bb4a0730322fb19
Source dataset
uspto-grants-2012_04
Patent number
US08153681B2

Reaction notes

Loading…