tert-Butyl 6-Oxa-3-azabicyclo(3.1.0)hexane-3-carboxylate → tert-butyl (3S,4R)-3-hydroxy-4-Methylpyrrolidine-1-carboxylate

HRID 252093Notes

Reaction equation

HRID 252093 reaction equation
[CH3:1][Li].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH:14]2[CH:12]([O:13]2)[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>C(OCC)C.[Cu]I>[C:3]([O:7][C:8]([N:10]1[CH2:11][C@@H:12]([CH3:1])[C@H:14]([OH:13])[CH2:15]1)=[O:9])([CH3:4])([CH3:5])[CH3:6]

Participants

5

Reactant 2

HCID 10103880tert-Butyl 6-Oxa-3-azabicyclo(3.1.0)hexane-3-carboxylateHCID 178418348HCID 178418348, compound

Product 1

HCID 53302312tert-butyl (3S,4R)-3-hydroxy-4-Methylpyrrolidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-10 °C

Procedure

Cool down a suspension of copper (I) iodide (1 g, 5.5 mmol) in dry diethyl ether (13 mL) under nitrogen to −10° C. with a saturated aqueous sodium chloride/ice bath and add methyllithium (1.6 M in diethyl ether, 6.8 mL, 10.9 mmol) dropwise to maintain the temperature at −10° C. Stir for 20 min at this temperature and add a solution of 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (430 mg, 2.32 mmol) in dry diethyl ether (5 mL). Stir for 1 h at −10° C. then add water (5 mL) dropwise and dichloromethane (5 mL), filter the resulting mixture through a pad of Celite® and wash thoroughly with dichloromethane. Separate the aqueous and organic phases and extract with 30:70 isopropanol:chloroform and wash with saturated aqueous sodium chloride, dry (magnesium sulfate) and concentrate to give trans-3-hydroxy-4-methylpyrrolidine-1-carboxylic acid tert-butyl ester which can be used without further purification (360 mg, 77%). 1H NMR (300 MHz, CDCl3) δ 3.84-3.91 (1H, m), 3.48-3.62 (2H, m), 3.10-3.23 (1H, m), 2.88-3.02 (1H, m), 1.98-2.12 (1H, m), 1.39 (9H, s), 0.95 (3H, d, J=6.97 Hz), MS (ES): m/z=224 [M+Na].

Workup

  1. stirringStir for 1 h at −10° C.
  2. filtrationadd water (5 mL) dropwise and dichloromethane (5 mL), filter the resulting mixture through a pad of Celite®
  3. washwash thoroughly with dichloromethane
  4. customSeparate the aqueous and organic phases
  5. extractionextract with 30:70 isopropanol
  6. washchloroform and wash with saturated aqueous sodium chloride
  7. dry with materialdry (magnesium sulfate)
  8. concentrationconcentrate

Sources & evidence

ORD record
ord-24ef91c8734c4b9283ad3feb5e8b1090
Source dataset
uspto-grants-2011_01
Patent number
US07868014B2

Reaction notes

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