Acetic Acid → 1-allyl 3-tert-butyl (2S)-4-hydroxy-2-[(methoxymethoxy)methyl]-1,3-pyrrolidinedicarboxylate

HRID 1374432Notes

Reaction equation

HRID 1374432 reaction equation
CC(C)([O-])C.[K+].[CH2:7]([O:10][C:11]([N:13]([CH2:28][C:29]([O:31]C)=O)[C@H:14]([CH2:23][O:24][CH2:25][O:26][CH3:27])[CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[O:12])[CH:8]=[CH2:9].Cl.[Cl-].[Na+].C(O)(=O)C.C([BH3-])#N.[Na+]>C1COCC1.CO>[OH:31][CH:29]1[CH2:28][N:13]([C:11]([O:10][CH2:7][CH:8]=[CH2:9])=[O:12])[C@H:14]([CH2:23][O:24][CH2:25][O:26][CH3:27])[CH:15]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17]

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 5003444Sodium cyanoborohydrideHCID 23665647Potassium tert-butoxideHCID 86592529tert-butyl (3S)-3-[[(allyloxy)carbonyl](2-methoxy-2-oxoethyl)amino]-4-(methoxymethoxy)butanoate

Product 1

HCID 865925281-allyl 3-tert-butyl (2S)-4-hydroxy-2-[(methoxymethoxy)methyl]-1,3-pyrrolidinedicarboxylateYield 30.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

To a suspension of potassium tert-butoxide (3.14 g, 28 mmol) in THF (130 ml) heated at 60° C. was added tert-butyl (3S)-3-[[(allyloxy)carbonyl](2-methoxy-2-oxoethyl)amino]-4-(methoxymethoxy)butanoate (5.24 g, 14 mmol) in THF (50 ml) and the mixture was stirred for 5 minutes. After cooled to 0° C. the reaction mixture was poured into diluted hydrochloric acid (after confirming that pH was about 3), a saturated aqueous sodium chloride solution was added thereto and the mixture was extracted three times with ethyl acetate. The organic layer was washed with water, then a saturated aqueous sodium chloride solution and dried over magnesium sulfate. The solvent was removed in vacuo. To a solution of the residue (4.17 g) in methanol (100 ml) were added acetic acid (1.45 ml, 25 mmol) and sodium cyanoborohydride (1.06 g, 17 mmol) and the mixture was stirred at room temperature for 30 minutes. The solvent was removed in vacuo. The residue was purified with silica gel (60 g) chromatography (hexane/ethyl acetate=2/1→1/1) to give 1-allyl 3-tert-butyl (2S)-4-hydroxy-2-[(methoxymethoxy)methyl]-1,3-pyrrolidinedicarboxylate (1.47 g, 30%).

Workup

  1. temperatureAfter cooled to 0° C. the reaction mixture
  2. additionwas added
  3. extractionthe mixture was extracted three times with ethyl acetate
  4. washThe organic layer was washed with water
  5. dry with materiala saturated aqueous sodium chloride solution and dried over magnesium sulfate
  6. customThe solvent was removed in vacuo
  7. stirringthe mixture was stirred at room temperature for 30 minutes
  8. customThe solvent was removed in vacuo
  9. customThe residue was purified with silica gel (60 g) chromatography (hexane/ethyl acetate=2/1→1/1)

Sources & evidence

ORD record
ord-13a85f119c744a8fa1a045c7e30296ff
Source dataset
uspto-grants-2007_01
Patent number
US07163936B2

Reaction notes

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