Triethylamine → (S)-[3-diazo-1-(4-nitrobenzyl)-2-oxo-propyl]-carbamic acid tert-butyl ester

HRID 60061Notes

Reaction equation

HRID 60061 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.ClC(OCC(C)C)=O.[N+:38](=[CH2:40])=[N-:39]>C1COCC1.CCOCC>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1)[C:10](=[O:12])[CH:40]=[N+:38]=[N-:39])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9550DiazomethaneHCID 62365Isobutyl chloroformateHCID 7021882N-(tert-Butoxycarbonyl)-4-nitro-L-phenylalanine

Product 1

HCID 86617183(S)-[3-diazo-1-(4-nitrobenzyl)-2-oxo-propyl]-carbamic acid tert-butyl esterYield 82%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of 2-(S)-tert-butoxycarbonylamino-3-(4-nitrophenyl)-propionic acid, 1, (1.20 g, 4.0 mmol) in THF (20 mL) was added dropwise triethylamine (0.61 mL, 4.4 mmol) followed by iso-butyl chloroformate (0.57 mL, 4.4 mmol). The reaction mixture was stirred at 0° C. for 20 minutes and filtered. The filtrate was treated with an ether solution of diazomethane (˜16 mmol) at 0° C. The reaction mixture was stirred at room temperature for 3 hours then concentrated in vacuo. The resulting residue was dissolved in EtOAc and washed successively with water and brine, dried (Na2SO4), filtered and concentrated. The residue was purified over silica (hexane/EtOAc 2:1) to afford 1.1 g (82% yield) of the desired product as a slightly yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.16 (d, J=8.7 Hz, 2H), 7.39 (d, J=8.7 Hz, 2H), 5.39 (s, 1H), 5.16 (d, J=6.3 Hz, 1H), 4.49 (s, 1H), 3.25 (dd, J=13.8 and 6.6, 1H), 3.06 (dd, J=13.5 and 6.9 Hz, 1H), 1.41 (s, 9H).

Workup

  1. filtrationfiltered
  2. stirringThe reaction mixture was stirred at room temperature for 3 hours
  3. concentrationthen concentrated in vacuo
  4. dissolutionThe resulting residue was dissolved in EtOAc
  5. washwashed successively with water and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified over silica (hexane/EtOAc 2:1)

Sources & evidence

ORD record
ord-4dbbd4c7e9c0463e977526341d36d8ee
Source dataset
uspto-grants-2016_09
Patent number
US09440963B2

Reaction notes

Loading…