Sodium Hydroxide → HCID 86673844, compound

HRID 1527397Notes

Reaction equation

HRID 1527397 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@:11]([CH2:14][N:15]=[N+:16]=[N-:17])([F:13])[CH2:10][C@H:9]1[C:18]([O:20]CC1C=CC=CC=1)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].[Br:30][C:31]1[CH:32]=[C:33]([C@H:37]([NH2:40])[CH2:38][F:39])[CH:34]=[CH:35][CH:36]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CO.O.CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@:11]([CH2:14][N:15]=[N+:16]=[N-:17])([F:13])[CH2:10][C@H:9]1[C:18](=[O:20])[NH:40][C@@H:37]([C:33]1[CH:34]=[CH:35][CH:36]=[C:31]([Br:30])[CH:32]=1)[CH2:38][F:39])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 28820355HCID 28820355, compoundHCID 86673843HCID 86673843, compound

Product 1

HCID 86673844HCID 86673844, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2S,4R)-4-azidomethyl-4-fluoro-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester (500 mg, 1.32 mmol) in methanol (20 mL), 1M sodium hydroxide (2.64 mL, 2.64 mmol) was added. The solution was stirred for 2 hours at RT then was diluted with water, the methanol was removed under reduced pressure. The aqueous layer was washed with Et2O (2×100 mL). The aqueous layer was acidified until pH 3 with 2N HCl and extracted with EtOAc (2×100 mL), dried with Na2SO4, filtered and concentrated. To the residue (100 mg, 0.34 mmol), (S)-1-(3-bromo-phenyl)-2-fluoro-ethylamine (described in Part C) (83 mg, 0.38 mmol) and HBTU (197 mg, 0.52 mmol) in DMF (5 mL) was added DIPEA (0.12 mL, 0.69 mmol). The reaction mixture was stirred for 16 h at RT then poured into water and extracted with EtOAc. The organic layer was dried with Na2SO4, filtered and concentrated. Purification by flash column chromatography on silica gel (c-hexane/EtOAc 1:1). MS (UPLC/MS): 488 [M+H]+, 532 [M+HCOO]−; tR (HPLC conditions f): 2.32 min.

Workup

  1. customthe methanol was removed under reduced pressure
  2. washThe aqueous layer was washed with Et2O (2×100 mL)
  3. extractionextracted with EtOAc (2×100 mL)
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. stirringThe reaction mixture was stirred for 16 h at RT
  8. extractionextracted with EtOAc
  9. dry with materialThe organic layer was dried with Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification by flash column chromatography on silica gel (c-hexane/EtOAc 1:1)
  13. custom2.32 min.

Sources & evidence

ORD record
ord-2da5e70005c845d0881a1c531f61d0b8
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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