Hydrochloric Acid → di-tert-butyl (4S)-N-(tert-butoxycarbonyl)-4-prop-2-yn-1-yl-L-glutamate

HRID 591341Notes

Reaction equation

HRID 591341 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:10][CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:37][C:38]#[C:39][Si](C)(C)C.Cl.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.ClCCl.CO.O>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:10][C@H:11]([CH2:39][C:38]#[CH:37])[C:12]([O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[O:13])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 6425893-Bromo-1-(trimethylsilyl)-1-propyneHCID 2733832Lithium HexamethyldisilazideHCID 86647571Di-tert-butyl Boc-L-glutamate

Product 1

HCID 117812721di-tert-butyl (4S)-N-(tert-butoxycarbonyl)-4-prop-2-yn-1-yl-L-glutamate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
-78 °C

Procedure

Di-tert-butyl N-(tert-butoxycarbonyl)-L-glutamate (633 mg, 1.76 mmol) was dissolved in tetrahydrofuran (6 ml) and at −78° C., lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran, 3.87 ml) were added dropwise. After 30 min, 3-bromo-1-(trimethylsilyl)-1-propyne (370 mg, 1.94 mmol) in tetrahydrofuran (2 ml) was added dropwise and the mixture was stirred at −78° C. for 3 h. The reaction was than warmed to 0° C. and 10 ml of 1 N hydrochloric acid were added. The mixture was extracted with dichloromethane, dried and concentrated in vacuo. The residue was purified by silica gel chromatography to give the intermediate TMS-protected alkyne. The intermediate was dissolved in 30 ml dichloromethane/methanol (1:1). Potassium carbonate (1 g) was added and the mixture was stirred for 1 h. Water (20 ml) was added and the mixture was extracted with dichloromethane, dried and concentrated in vacuo. The product (416 mg, 59%) was used in the following reaction without further purification.

Workup

  1. temperaturethan warmed to 0° C.
  2. extractionThe mixture was extracted with dichloromethane
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel chromatography
  6. customto give the intermediate TMS-protected alkyne
  7. stirringthe mixture was stirred for 1 h
  8. extractionthe mixture was extracted with dichloromethane
  9. customdried
  10. concentrationconcentrated in vacuo
  11. customThe product (416 mg, 59%) was used in the following reaction without further purification

Sources & evidence

ORD record
ord-76690c7fa41645609238e4283c3634a0
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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