Azidotrimethylsilane → HCID 86667778, compound

HRID 1484482Notes

Reaction equation

HRID 1484482 reaction equation
[N:1]([Si](C)(C)C)=[N+:2]=[N-:3].C[Si](C)(C)[O:10][CH2:11][C:12]1[CH:21]=[CH:20][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][CH:13]=1.O=[CH:25][CH2:26][CH2:27][NH:28][C:29](=[O:34])[C:30]([F:33])([F:32])[F:31]>CC#N>[N:1]([CH:25]([O:10][CH2:11][C:12]1[CH:21]=[CH:20][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][CH:13]=1)[CH2:26][CH2:27][NH:28][C:29](=[O:34])[C:30]([F:33])([F:32])[F:31])=[N+:2]=[N-:3]

Participants

5

Reactant 3

HCID 78378AzidotrimethylsilaneHCID 14183813HCID 14183813, compoundHCID 22357954HCID 22357954, compound

Product 1

HCID 86667778HCID 86667778, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
-40 °C

Procedure

A solution of azidotrimethylsilane (0.93 mL; 7.1 mmol) and methyl 4-[(trimethylsiloxy)methyl]benzoate (1.35 g; 5.7 mmol) in anhydrous MeCN (3 mL) was added dropwise to a solution of N-(3-oxopropyl)trifluoroacetamide (0.8 g; 4.7 mmol) containing a catalytic amount of anhydrous ferric chloride (38 mg; 0.2 mmol) in anhydrous MeCN (10 mL) cooled to −40° C. The mixture was stirred at −40° C. for 90 min and the reaction quenched with phosphate buffered saline (pH 7.4). The aqueous phase was extracted with DCM. The combined organic layers were washed with brine, dried (MgSO4), filtrated and evaporated. The residue was purified by silica column chromatography (DCM:Hex:EtOAc, 6:3:1) and the methyl 4-[(3-amino-1-azidopropoxy)methyl]benzoate was obtained as a clear viscous liquid, which solidified upon prolonged standing in a yield of 0.95 g (56%). 1H-NMR (500 MHz, CDCl3): δ=2.04-2.14 ppm (m, 2H), 3.40-3.47 ppm (m, 1H), 3.56-3.64 ppm (m, 1H), 3.92 ppm (s, 3H), 4.63 ppm (d, J=12.0 Hz, 1H), 4.66 ppm (dd, J=6.0, 4.5 Hz, 1H), 4.90 ppm (d, J=12.0 Hz, 1H), 6.89 ppm (bs, 1H, NH), 7.41 ppm (d, J=8.5 Hz, 2H), 8.04 ppm (d, J=8.5 Hz, 2H); 13C-NMR (500 MHz, CDCl3): δ=33.94, 35.83, 52.29, 70.66, 90.46, 115.76 ppm (q, J=1146.5 Hz), 127.76, 130.02, 130.14, 141.30, 157.23 (q, J=148.0 Hz), 166.79 ppm. HRMS [+Scan]; calculated m/z for C12H19O3Si 239.1098; observed mass: 239.1095.

Workup

  1. customthe reaction quenched with phosphate buffered saline (pH 7.4)
  2. extractionThe aqueous phase was extracted with DCM
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltrated
  6. customevaporated
  7. customThe residue was purified by silica column chromatography (DCM:Hex:EtOAc, 6:3:1)

Sources & evidence

ORD record
ord-a99c02b184a7402794ead641cb3c21cf
Source dataset
uspto-grants-2016_08
Patent number
US09422232B2

Reaction notes

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