Ethyl Acetate → 1-Benzyl-3-(SR)-hydroxymethyl-4-(RS)-(3-thienyl)pyrrolidine

HRID 380461Notes

Reaction equation

HRID 380461 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2[CH:17]=[CH:16][S:15][CH:14]=2)[CH:10]([C:18](OC)=[O:19])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].CCOC(C)=O.[OH-].[Na+]>C1COCC1>[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2[CH:17]=[CH:16][S:15][CH:14]=2)[CH:10]([CH2:18][OH:19])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 69212355Methyl 1-benzyl-4-(thiophen-3-yl)pyrrolidine-3-carboxylate

Product 1

HCID 183647731-Benzyl-3-(SR)-hydroxymethyl-4-(RS)-(3-thienyl)pyrrolidineYield 97.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 0.55 g (1.84 mmol) of 1-benzyl-3-(SR)-carbomethoxy-4-(RS)-(3-thienyl)pyrrolidine in 30 mL of THF at 0° C. was added 1.84 mL (1.84 mmol) of a 1M solution of lithium aluminum hydride in THF and the reaction was stirred at rt for 12 h. To the reaction mixture was then added 5 mL of EtOAc and 2 mL of 2N NaOH. The reaction mixture was extracted with ether and the combined organic fractions were washed with 2N NaOH solution and sat'd NaCl. The organic fractions were dried over Na2SO4, filtered and the filtrate was concentrated to give 0.49 g of the title compound which was used without further purification. 1H NMR (CDCl3) δ7.28-7.36 (m, 7H), 7.03 (d, 1H, J=4.1 Hz), 3.66-3.78 (m, 5H).

Workup

  1. extractionThe reaction mixture was extracted with ether
  2. washthe combined organic fractions were washed with 2N NaOH solution
  3. dry with materialThe organic fractions were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-31c0d4018b1340759f8611ebfef12bab
Source dataset
uspto-grants-2001_10
Patent number
US06303593B1

Reaction notes

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