Tetrahydrofuran → HCID 66927228, compound

HRID 712802Notes

Reaction equation

HRID 712802 reaction equation
O=[C:2]1[N:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@@H:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:4][CH2:3]1.C1COCC1.CCN(C(C)C)C(C)C.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O>C1(C)C=CC=CC=1.CN(C1C=CN=CC=1)C.CCOC(C)=O.O>[N:6]1([C:7]([O:9][C:10]([CH3:11])([CH3:13])[CH3:12])=[O:8])[CH:2]=[CH:3][CH2:4][C@@H:5]1[C:14]([O:16][CH2:17][CH3:18])=[O:15]

Participants

9

Reactant 4

HCID 8028TetrahydrofuranHCID 9845Trifluoroacetic anhydrideHCID 81531DiisopropylethylamineHCID 8208851-Boc-D-Pyroglutamic acid ethyl ester

Product 1

HCID 66927228HCID 66927228, compoundYield 77.6%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-45 °C

Procedure

To a solution of (R)-1-tert-butyl 2-ethyl 5-oxopyrrolidine-1,2-dicarboxylate (D24) (14.3 g, 55.58 mmol) in toluene (100 ml) cooled at −50° C., LiEt3BH 1M sol in THF (58.4 ml, 58.36 mmol) was added dropwise maintaining the reaction temperature below −45° C. After complete addition the mixture was stirred at −45° C. for 30 min. DIPEA (42 ml, 239 mmol), DMAP (102 mg, 0.83 mmol) and TFAA (8.9 ml, 63.92 mmol) were added sequentially maintaining the reaction temperature below −45° C. After complete addition, the reaction mixture was warmed to 20-25° C. within one hour and kept for an additional 2 hrs at this temperature. The reaction mixture was slowly charged with water (8 ml) so that the temperature did not exceed 5° C. and diluted with EtOAc (50 ml). Aqueous and organic phases were then separated and the organics washed again with water (8 ml), dried over Na2SO4 and evaporated to obtain residue which was purified by Biotage SNAP-Si cartridge (50 g) eluting with cHex/EtOAc from 90/10 to 50/50. Collected fractions, after solvent evaporation afforded the title compound (D25) (10.4 g).

Workup

  1. additionwas added dropwise
  2. temperaturemaintaining the reaction temperature below −45° C
  3. additionAfter complete addition the mixture
  4. temperaturemaintaining the reaction temperature below −45° C
  5. additionAfter complete addition
  6. temperaturethe reaction mixture was warmed to 20-25° C. within one hour
  7. waitkept for an additional 2 hrs at this temperature
  8. customdid not exceed 5° C.
  9. customAqueous and organic phases were then separated
  10. washthe organics washed again with water (8 ml)
  11. dry with materialdried over Na2SO4
  12. customevaporated
  13. customto obtain residue which
  14. customwas purified by Biotage SNAP-Si cartridge (50 g)
  15. washeluting with cHex/EtOAc from 90/10 to 50/50
  16. customCollected fractions, after solvent evaporation

Sources & evidence

ORD record
ord-1678e5487d00451ea9debf7c197a276d
Source dataset
uspto-grants-2015_11
Patent number
US09181279B2

Reaction notes

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