Acetic Acid → carbonic acid (2S,4S)-2-tert-butylcarbonylamino-4-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-5-methyl-hexylester tert-butyl ester

HRID 604979Notes

Reaction equation

HRID 604979 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([O:10][CH2:11][CH2:12][CH2:13][O:14][CH3:15])[CH:3]=1.C([Li])[CH2:17][CH2:18][CH3:19].C(O[C:26]([N:28]1[C@H:32]([CH2:33][O:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][C@@H:30]([CH:42]([CH3:44])[CH3:43])[C:29]1=[O:45])=[O:27])(C)(C)C.[C:46](O)(=O)C>O1CCCC1.CCCCCC>[C:38]([O:37][C:35](=[O:36])[O:34][CH2:33][C@@H:32]([NH:28][C:26]([C:18]([CH3:17])([CH3:19])[CH3:46])=[O:27])[CH2:31][C@H:30]([C:29](=[O:45])[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([O:10][CH2:11][CH2:12][CH2:13][O:14][CH3:15])[CH:3]=1)[CH:42]([CH3:43])[CH3:44])([CH3:39])([CH3:40])[CH3:41]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 214587114-Bromo-1-methoxy-2-(3-methoxypropoxy)benzeneHCID 58298428(3S,5S)-5-tert-butoxycarbonyloxymethyl-3-isopropyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 178418339Butyllithium

Product 1

HCID 66813799carbonic acid (2S,4S)-2-tert-butylcarbonylamino-4-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-5-methyl-hexylester tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 7.9 g of 4-bromo-1-methoxy-2-(3-methoxypropoxy)-benzene in 125 mL of tetrahydrofuran is cooled to −78° C. A solution of n-butyllithium (14.219 g of a 1.6 M solution in hexane) is added within 50 minutes. The reaction mixture is stirred for 90 minutes at −78° C. and treated slowly with 75 mL of a tetrahydrofuran solution of 8.93 g of (3S,5S)-5-tert-butoxycarbonyloxymethyl-3-isopropyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester. The resulting reaction mixture is stirred for 3 hours at −78° C. Finally the temperature is raised to −40° C. and the mixture stirred for 45 minutes. Acetic acid (4 mL) was added and the solvent removed by evaporation. The residue is dissolved in 100 mL of ethyl acetate and washed with two 75 mL portions of saturated sodium bicarbonate solution followed by one portion of 150 mL of water. The organic phase was dried and the solvent removed to give an oil. Chromatography on silica-gel, eluting with hexane/ethyl acetate gives, after combination of the product containing fractions and removal of the solvent, affords the title compound as an oil.

Workup

  1. customThe resulting reaction mixture
  2. stirringis stirred for 3 hours at −78° C
  3. temperatureFinally the temperature is raised to −40° C.
  4. stirringthe mixture stirred for 45 minutes
  5. customthe solvent removed by evaporation
  6. dissolutionThe residue is dissolved in 100 mL of ethyl acetate
  7. washwashed with two 75 mL portions of saturated sodium bicarbonate solution
  8. customThe organic phase was dried
  9. customthe solvent removed
  10. customto give an oil
  11. washChromatography on silica-gel, eluting with hexane/ethyl acetate
  12. customgives
  13. additionafter combination of the product containing
  14. customfractions and removal of the solvent

Sources & evidence

ORD record
ord-847174e14a1a4d5bbfb979bedb681052
Source dataset
uspto-grants-2011_03
Patent number
US07910774B2

Reaction notes

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