Hydrochloric Acid → Tert-butyl 4-hydroxy-2-(methoxymethyl)pyrrolidine-1-carboxylate

HRID 1071500Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([O:13]CC2C=CC=CC=2)[CH2:10][CH:9]1[CH2:21][O:22]S(C)(=O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].[B-](CC)(CC)[CH2:29]C.Cl.CCCCCC.C(OCC)(=O)C>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([OH:13])[CH2:10][CH:9]1[CH2:21][O:22][CH3:29])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: 0 °C

Procedure

The 4-benzyloxy-2-methanesulfonyloxymethyl-pyrrolidine-1-carboxylic acid t-butyl ester (234.14 mg, 0.65 mmol) was taken up in anhydrous THF under argon and cooled to 0° C. Super-Hydride (1.0M, 0.98 mmol, 0.98 mL) was added via a syringe over 10 min. The solution was stirred for 1 h at 0° C., the TLC indicated that no starting material remained. The reaction mixture 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. (4:1 hexane-ethyl acetate) Yield 168.57 mg. 1H NMR (CDCl3, 300 MHz): δ 1.22 (d, J=9.0 Hz, 3H), 1.44 (s, 9H), 1.65-1.77 (m, 1H), 2.13-2.24 (m, 1H), 3.45 (dd, J=7, 12 Hz, 1H), 3.61 (d, J=7 Hz, 1H), 3.94-4.04 (m, 1H), 4.50 (s, 2H), 7.27-7.39 (m, 5H).

Workup

extractionthe aqueous layer was extracted three times with ethyl acetate
washThe combined organic layers were washed with water and brine
dry with materialthen dried over MgSO4
filtrationThe solution was filtered
customthe solvent removed under reduced pressure
customThe product was isolated by flash chromatography

Sources & evidence

ORD record: ord-8e4b5fbd8392430abfc6fe29088cf579
Source dataset: uspto-grants-2005_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06906067B2

Reaction notes

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