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

HRID 1454260Notes

Reaction equation

HRID 1454260 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

6

Reactant 4

HCID 313Hydrochloric AcidHCID 208006634-Benzyloxy-2-methanesulfonyloxymethyl-pyrrolidine-1-carboxylic Acid T-butyl EsterHCID 21226206Ethyl acetate hexaneHCID 23712863Lithium triethylborohydride

Product 1

HCID 19900165Tert-butyl 4-hydroxy-2-(methoxymethyl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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 0EC. 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 0EC, 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

  1. temperaturecooled to 0EC
  2. extractionthe aqueous layer was extracted three times with ethyl acetate
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialthen dried over MgSO4
  5. filtrationThe solution was filtered
  6. customthe solvent removed under reduced pressure
  7. customThe product was isolated by flash chromatography

Sources & evidence

ORD record
ord-f24d92c5199d4f80a64bf1f7dbc743c9
Source dataset
uspto-grants-2009_01
Patent number
US07479495B2

Reaction notes

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