Diisopropylamine → HCID 18625566, compound

HRID 1859407Notes

Reaction equation

HRID 1859407 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]1([CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:16][CH2:15]1.[Cl-].[NH4+].C1C[O:29]CC1>CCCCCC.CCOC(C)=O>[OH:29][CH:18]([CH2:17][C:14]1([CH3:13])[CH2:15][CH2:16]1)[C:19]([O:21][CH2:22][CH3:23])=[O:20]

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 22235737HCID 22235737, compoundHCID 178418339Butyllithium

Product 1

HCID 18625566HCID 18625566, compound

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of diisopropylamine (1.9 mL, 13 mmol) in dry THF (20 mL) at 0° C. under inert atmosphere was added n-butyllithium (5.2 mL of a 2.5 M solution in hexane, 13 mmol) dropwise over a period of 5 min. The solution was cooled to −78 ° C. and ethyl 3-(1-methyl-cyclopropyl)propanoate (1.87 g, 12 mmol) was added dropwise over a period of 5 min. The solution was stirred at −78 ° C. for 1 h at which time (+)-camphorsulfonyloxaziridine (3.5 g, 15 mmol) was added all at once. The resulting suspension was stirred at −78 ° C. for 30 min and then allowed to warm to ambient temperature over 30 min. EtOAc (50 mL) and saturated aqueous ammonium chloride (25 mL) were added and the organic layer was separated and washed with water (20 mL), dried (MgSO4), and filtered. The solvents were removed under reduced pressure and the resulting oily solid was stirred in ether (15 mL) for 30 min. The solid was removed by filtration and the filtrate solvent was removed under reduced pressure. The residue was purified by flash column chromatography using a gradient elution of 10% to 15% EtOAc in hexanes to give ethyl 2-hydroxy-3-(1-methyl-cyclopropyl)propanoate as a colorless liquid. TLC Rf=0.5 (20% EtOAc-hexanes); HPLC RT=2.73 min (Method A); 1H NMR 400 MHz, CDCl3, 4.31 ppm (M, 1H)4.23 ppm (m, 2H), 2.65 ppm (d, J=6.1 Hz, 1H), 1.76 ppm (dd, J=4.2, 14.6 Hz, 1H), 1.54 ppm (dd, J=8.4, 14.6 Hz, 1H), 1.30 (t, J=8 Hz, 3H), 1.14 ppm (s, 3H), 0.42 ppm (m. 1H), 0.30 ppm (m, 3H)

Workup

  1. additionwas added all at once
  2. temperatureto warm to ambient temperature over 30 min
  3. customthe organic layer was separated
  4. washwashed with water (20 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customThe solvents were removed under reduced pressure
  8. stirringthe resulting oily solid was stirred in ether (15 mL) for 30 min
  9. customThe solid was removed by filtration
  10. customthe filtrate solvent was removed under reduced pressure
  11. customThe residue was purified by flash column chromatography
  12. washa gradient elution of 10% to 15% EtOAc in hexanes

Sources & evidence

ORD record
ord-cab11128e377478c9d17686fcf0aa128
Source dataset
uspto-grants-2003_03
Patent number
US06528503B2

Reaction notes

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