Triethylamine → HCID 69195805, compound

HRID 898355Notes

Reaction equation

HRID 898355 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:9][C@H:10]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C@H:11]2[CH2:13][O:12]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH2:27][NH2:28].CCN(CC)CC.[CH2:39]([O:46][C:47](Cl)=[O:48])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C(O)(C)C.CCOC(C)=O.C1COCC1>[CH2:39]([O:46][C:47](=[O:48])[N:28]([CH2:13][CH:11]([OH:12])[CH:10]([NH:14][C:15]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:21])[CH2:9][C:4]1[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=1)[CH2:27][C:26]1[CH:29]=[CH:30][CH:31]=[C:24]([O:23][CH3:22])[CH:25]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 211563-MethoxybenzylamineHCID 9922319tert-Butyl ((S)-2-(3,5-difluorophenyl)-1-((S)-oxiran-2-yl)ethyl)carbamate

Product 1

HCID 69195805HCID 69195805, compoundYield 70%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A mixture of tert-butyl (1S)-2-(3,5-difluorophenyl)-1-[(2S)-oxiran-2-yl]ethylcarbamate (1.0 g, 3.3 mmol) and 3-methoxybenzylamine (1.8 g, 13.3 mmol) in isopropyl alcohol (30 ml) was stirred at room temperature for 6.5 h. The reaction mixture was diluted with EtOAc (100 ml) and washed with 1 N HCl (3×30 ml), sat'd aq. NaHCO3 (1×50 ml) and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo to yield an off white solid. The residue was dissolved in THF (20 ml) and chilled to 0° C. followed by the addition of Et3N (0.6 ml, 4.4 mmol) and benzylchloroformate (0.5 ml, 3.6 mmol). The reaction mixture was warmed spontaneously for 3 h. The reaction mixture was diluted with EtOAc, washed with 1N HCl, NaHCO3, and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. Flash chromatography 30% EtOAC/Heptanes yields 1.3 g (70%) of [3-tert-butoxycarbonylamino-4-(3,5-difluoro-phenyl)-2-hydroxy-butyl]-(3-methoxybenzyl)-carbamic acid benzyl ester. MS (ESI+) for C31H36F2N2O6 m/z 570.8 (M+H)+.

Workup

  1. washwashed with 1 N HCl (3×30 ml)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customto yield an off white solid
  5. temperaturechilled to 0° C.
  6. temperatureThe reaction mixture was warmed spontaneously for 3 h
  7. washwashed with 1N HCl, NaHCO3, and brine
  8. dry with materialThe organic layer was dried over Na2SO4
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f6c7e2684aca400ab4771ee97f2039bf
Source dataset
uspto-grants-2008_04
Patent number
US07351738B2

Reaction notes

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