Hydrochloric Acid → (2S,4R)-tert-butyl 4-(benzyloxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylate

HRID 1071490Notes

Reaction equation

HRID 1071490 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][CH:9]1[C:21](O)=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.CCCCCC.C(OCC)(=O)C>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([O:13][CH2:14][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:10][CH:9]1[CH2:21][OH:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 41798284-(Benzyloxy)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acidHCID 21226206Ethyl acetate hexane

Product 1

HCID 14821718(2S,4R)-tert-butyl 4-(benzyloxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

The 4-benzyloxy-pyrrolidine-1,2-dicarboxylic acid 1-t-butyl ester (1.00 g, 3.11 mmol) was taken up in anhydrous THF under argon and cooled to 0° C. BH3 THF (1.0 M, 6.22 mmol, 6.22 mL) was added to the solution dropwise over 10 min. The reaction mixture was then allowed to stir at 0° C. for 30 min then warmed to room temp and stirred for an additional 30 min. The reaction was slowly poured into a 1N HCl solution and the aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with water and brine then dried over MgSO4. The solution was filtered and the solvent removed under reduced pressure. The product was isolated by flash chromatography. (1:1 hexane-ethyl acetate) Yield 814 mg. 1H NMR (CDCl3, 300 MHz): δ 1.48 (s, 9H), 1.63-1.76 (m, 1H), 2.10-2.26 (m, 1H), 3.33 (m, 1H), 3.50-3.60 (m, 1H), 3.63-3.75 (m, 2H), 4.05-4.19 (m, 2H), 4.49 (s, 2H), 7.23-7.39 (m, 5H).

Workup

  1. temperaturethen warmed to room temp
  2. stirringstirred for an additional 30 min
  3. extractionthe aqueous layer was extracted three times with ethyl acetate
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialthen dried over MgSO4
  6. filtrationThe solution was filtered
  7. customthe solvent removed under reduced pressure
  8. customThe product was isolated by flash chromatography

Sources & evidence

ORD record
ord-defba6d6061e4e9cbd332da3cfe6a295
Source dataset
uspto-grants-2005_06
Patent number
US06906067B2

Reaction notes

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