Trifluoroacetic acid → HCID 86726821, compound

HRID 1499604Notes

Reaction equation

HRID 1499604 reaction equation
[N:1]([CH2:4][C@H:5]([CH:29]1[CH2:31][CH2:30]1)[C@H:6]([C@H:15]1[CH2:19][O:18]C(C)(C)[N:16]1[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[O:7][Si:8]([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9])=[N+:2]=[N-:3].C(O)(C(F)(F)F)=O.CCN(C(C)C)C(C)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>CO>[N:1]([CH2:4][C@H:5]([CH:29]1[CH2:30][CH2:31]1)[C@@H:6]([OH:7])[C@H:15]([NH:16][C:22](=[O:23])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:19][OH:18])=[N+:2]=[N-:3].[N:1]([CH2:4][C@H:5]([CH:29]1[CH2:30][CH2:31]1)[C@@H:6]([O:7][Si:8]([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9])[C@H:15]([NH:16][C:22](=[O:23])[O:24][C:25]([CH3:28])([CH3:26])[CH3:27])[CH2:19][OH:18])=[N+:2]=[N-:3]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonateHCID 86726822HCID 86726822, compound

Product 2

HCID 86726820HCID 86726820, compoundYield 43%HCID 86726821HCID 86726821, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of tert-butyl (4R)-4-((1R,2S)-3-azido-1-{[tert-butyl(dimethyl)silyl]oxy}-2-cyclopropylpropyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate (1.16 g, 2.55 mmol) in MeOH (5 mL) was cooled on an ice bath, then TFA (4.9 mL, 64 mmol) was added. The reaction mixture was allowed to warm to ambient temperature and stirred for 30 min. The volatile organic solvents were removed under reduced pressure and the residue was azeotropically evaporated with toluene several times. The residue was then dissolved in anhydrous DCM (18 mL) and DIPEA (0.99 g, 7.6 mmol) and di-tert-butyl dicarbonate (0.84 g, 3.8 mmol) were added. The solution was stirred at ambient temperature for 4 h. The crude reaction mixture was concentrated under reduced pressure and the residue was purified by flash column chromatography (40 g silica gel, eluting with 0-100% EtOAc/DCM) to afford the desired product (0.33 g, 43%) and tert-butyl [(1R,2R,3S)-4-azido-2-{[tert-butyl(dimethyl)silyl]oxy}-3-cyclopropyl-1-(hydroxymethyl)butyl]carbamate (0.50 g, 50%). LCMS (ESI) calc. for C13H25N4O4 [M+H]+ m/z=301.2. found: 301.2. For tert-butyl [(1R,2R,3S)-4-azido-2-{[tert-butyl(dimethyl)silyl]oxy}-3-cyclopropyl-1-(hydroxymethyl)butyl]carbamate: LCMS (ESI) calc. for C19H38N4O4SiNa [M+Na]+ m/z=437.3. found 437.0

Workup

  1. customThe volatile organic solvents were removed under reduced pressure
  2. customthe residue was azeotropically evaporated with toluene several times
  3. dissolutionThe residue was then dissolved in anhydrous DCM (18 mL)
  4. stirringThe solution was stirred at ambient temperature for 4 h
  5. customThe crude reaction mixture
  6. concentrationwas concentrated under reduced pressure
  7. customthe residue was purified by flash column chromatography (40 g silica gel, eluting with 0-100% EtOAc/DCM)

Sources & evidence

ORD record
ord-fbb50033b8e0497f8e423664d53487dc
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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