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

HRID 1690082Notes

Reaction equation

HRID 1690082 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.C([Li])CCC.[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:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][CH:3]=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

To a solution of commercially available (Sigma Aldrich Ltd.) 1-bromo-4-[(phenylmethyl)oxy]benzene (390 mg, 1.48 mmol) in dry THF (2 ml) at −78° C., under nitrogen atmosphere, was added dropwise n-butyllithium 1.6M solution in hexanes (0.88 ml, 1.4 mmol). 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 a saturated aqueous ammonium chloride solution. The mixture was diluted with water and extracted with ethyl acetate. The organic phase was then washed with brine, dried (Na2SO4), and evaporated under vacuo to give the crude material, which was then purified by chromatography on silica gel eluting with cyclohexane:ethyl acetate (95:5), thus affording the title compound as a white solid (170 mg, 32%); Rf (cyclohexane:ethyl acetate 8:2): 0.30; 1H NMR (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 a saturated aqueous 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 (Na2SO4)
  8. customevaporated under vacuo
  9. customto give the crude material, which
  10. customwas then purified by chromatography on silica gel eluting with cyclohexane:ethyl acetate (95:5)

Sources & evidence

ORD record
ord-70778abe17324c479e04aef45b4191dd
Source dataset
uspto-grants-2012_04
Patent number
US08153623B2

Reaction notes

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