Water → HCID 53255231, compound

HRID 1926711Notes

Reaction equation

HRID 1926711 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:25]([O:27]CC(F)(F)F)=[O:26])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][C:18]([F:21])([F:20])[F:19])[C:12]=1[N+:22]([O-:24])=[O:23])=[O:7])([CH3:4])([CH3:3])[CH3:2].O.C(N(CC)CC)C.O(C(OC(C)(C)C)=O)C(OC(C)(C)C)=O>O1CCOCC1>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:25]([OH:27])=[O:26])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][C:18]([F:21])([F:20])[F:19])[C:12]=1[N+:22]([O-:24])=[O:23])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 53254529HCID 53254529, compound

Product 1

HCID 53255231HCID 53255231, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

2,2,2-Trifluoroethyl N-(tert-butoxycarbonyl)-2-nitro-3-(trifluoromethoxy)-L-phenylalaninate (121) 2-Nitro-3-(trifluoromethoxy)-L-phenylalanine, hydrochloride salt (119) (250.6 mg, 0.758 mmol) was suspended in dioxane (3.5 mL)/water (3.5 mL) and the mixture was cooled to 0° C. Triethylamine (0.368 mL, 2.65 mmol) was added, resulting in a solution. BOC2O (199 mg, 0.910 mmol) was added and the mixture was stirred at 0° C. for 15 min, then allowed to warm to RT. After 2 h at RT, most of the dioxane was removed by evaporation under reduced pressure, and saturated aqueous ammonium chloride solution was added until the pH was lowered to −3. The mixture was diluted with EtOAc (10 mL), and the aqueous layer was extracted with EtOAc (3×15 mL). The combined extracts were dried over sodium sulfate, filtered and evaporated in vacuo to give N-(tert-butoxycarbonyl)-2-nitro-3-(trifluoromethoxy)phenylalanine (120), which was dissolved in dichloromethane (7 mL). 1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (98%, 0.195 mL, 0.874 mmol), N,N-dimethylpyridin-4-amine (97%, 45.7 mg, 0.363 mmol) and 2,2,2-trifluoroethanol (99%, 0.106 mL, 1.46 mmol) were added and the resulting mixture was stirred for 18 h at RT. The reaction mixture was washed with saturated aqueous sodium chloride solution, and the aqueous layer was extracted with dichloromethane (3×5 mL). The combined organic layers were dried, filtered and concentrated in vacuo. Purification using silica gel chromatography (Gradient: 0% to 30% EtOAc in heptane) provided the product as a white solid (170.3 mg, 47% over 2 steps). LCMS m/z 475.4 (M−1). 1H NMR (400 MHz, DMSO-d6) δ 1.33 (s, 9H), 3.01-3.12 (m, 2H), 4.32-4.39 (m, 1H), 4.69-4.79 (m, 2H), 7.57-7.66 (m, 3H), 7.74 (dd, J=8.2, 8.2 Hz, 1H).

Workup

  1. customresulting in a solution
  2. temperatureto warm to RT
  3. waitAfter 2 h at RT
  4. custommost of the dioxane was removed by evaporation under reduced pressure, and saturated aqueous ammonium chloride solution
  5. additionwas added until the pH
  6. additionThe mixture was diluted with EtOAc (10 mL)
  7. extractionthe aqueous layer was extracted with EtOAc (3×15 mL)
  8. dry with materialThe combined extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-07443011c3e84d148380c6ded63864f9
Source dataset
uspto-grants-2012_05
Patent number
US08183238B2

Reaction notes

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