Hydrochloric Acid → ethyl (3S,4S)-4-t-butoxycarbonylamino-3-hydroxy-6-methylheptanoate

HRID 1761622Notes

Reaction equation

HRID 1761622 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.CCCCCC.[C:19]([O:22][CH2:23][CH3:24])(=[O:21])[CH3:20].[C:25]([NH:32][C@H:33]([CH:38]=[O:39])[CH2:34][CH:35]([CH3:37])[CH3:36])([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26].Cl>O1CCCC1>[NH:32]([C:25]([O:27][C:28]([CH3:30])([CH3:29])[CH3:31])=[O:26])[C@H:33]([C@H:38]([CH2:20][C:19]([O:22][CH2:23][CH3:24])=[O:21])[OH:39])[CH2:34][CH:35]([CH3:37])[CH3:36]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 8058HexaneHCID 8857Ethyl AcetateHCID 104275tert-butyl N-[(2S)-4-methyl-1-oxopentan-2-yl]carbamateHCID 178418339Butyllithium

Product 1

HCID 11347225ethyl (3S,4S)-4-t-butoxycarbonylamino-3-hydroxy-6-methylheptanoateYield 38.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
10 °C

Procedure

To diisopropylamine (7.7 gm, 0.077 mole) in dry tetrahydrofuran (26 mL) cooled to -20° C. under an argon atmosphere was added dropwise n-butyllithium in hexane (1.46 m, 52.4 mL, 0.077 mole). The solution was stirred 15 minutes, the temperature lowered to -78° C. and dry ethyl acetate (6.7 g. 0.077 mole) added dropwise while maintaining the temperature below -75° C. The solution was stirred 10 minutes and a precooled (-78° C.) tetrahydrofuran solution of Boc-L-leucinal (11 gm., 0.051 mole) was added. After 30 minutes, 2M HCl (40 mL) was added and the mixture was slowly warmed to 10° C. and extracted with ether (3×200 mL). The combined ethereal extract was washed with saturated sodium chloride (NaCl) and dried with magnesium sulfate (MgSO4) and filtered. Evaporation of the filtrate in vacuo gave 14 gm of crude product which was purified by flash column chromatography (20% ethylacetate in hexane). Obtained 6 gm of Boc-Sta-OEt.

Workup

  1. customlowered to -78° C.
  2. temperaturewhile maintaining the temperature below -75° C
  3. stirringThe solution was stirred 10 minutes
  4. waitAfter 30 minutes
  5. extractionextracted with ether (3×200 mL)
  6. extractionThe combined ethereal extract
  7. washwas washed with saturated sodium chloride (NaCl)
  8. dry with materialdried with magnesium sulfate (MgSO4)
  9. filtrationfiltered
  10. customEvaporation of the filtrate in vacuo
  11. customgave 14 gm of crude product which
  12. customwas purified by flash column chromatography (20% ethylacetate in hexane)

Sources & evidence

ORD record
ord-ee69150ae5d04e4e982217e2a3054a28
Source dataset
uspto-grants-1989_05
Patent number
US04826958

Reaction notes

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