Sodium Azide → Tert-butyl 2-hydroxy-3-[(2-pyridinylsulfonyl)amino]propylcarbamate

HRID 1182278Notes

Reaction equation

HRID 1182278 reaction equation
[O:1]1[CH2:3][CH:2]1[CH2:4][NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9].[N-]=[N+]=[N-].[Na+].[N:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[S:23](Cl)(=[O:25])=[O:24].C([N:30](CC)C(C)C)(C)C>CN(C)C=O.ClCCl>[OH:1][CH:2]([CH2:3][NH:30][S:23]([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][N:17]=1)(=[O:25])=[O:24])[CH2:4][NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9]

Participants

7

Reactant 4

HCID 33557Sodium AzideHCID 81531DiisopropylethylamineHCID 3787675Pyridine-2-sulfonyl ChlorideHCID 11062891tert-Butyl N-(2-oxiranylmethyl)carbamate

Product 1

HCID 58981687Tert-butyl 2-hydroxy-3-[(2-pyridinylsulfonyl)amino]propylcarbamateYield 6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
65 °C

Procedure

First, 21 g (121 mmol) of tert-butyl 2-oxiranylmethylcarbamate was dissolved in 90 mL of dimethylformamide and 11.8 g (182 mmol) of sodium azide was added. The reaction mixture was stirred at 65° C. overnight. The dimethylformamide was removed and ether was added. The ether layer was washed with brine (3×), dried over anhydrous magnesium sulfate, and concentrated. The residue was dissolved in 50 mL of methanol and hydrogenated with 2 g of 10% palladium on carbon under 45 psi of hydrogen gas at room temperature overnight. The catalyst was removed by filtration and the filtrate was concentrated. The residue was dissolved in 30 mL of dichloromethane, and 17.7 mL (17.7 mmol) of 1M 2-pyridinylsulfonyl chloride in dichloromethane and 3.8 mL (21.8 mmol) of N,N-diisopropylethylamine were added. The reaction mixture was stirred at room temperature overnight. After removal of solvent, purification by column chromatography with hexane:ethyl acetate (1:2) as eluant gave 350 mg (0.9%) of tert-butyl 2-hydroxy-3-[(2-pyridinylsulfonyl)amino]propylcarbamate. 1H-NMR (300 MHz CDCl3): δ 8.72 (d, J=6 Hz, 1H), 8.05 (d, J=8 Hz, 1H), 7.97 (t, J=8 Hz, 1H), 7.55 (m, 1H), 6.10 (br s, 1H), 5.11 (br s, 1H), 4.33 (d, J=5 Hz, 1H), 3.81 (m, 1H), 3.36–3.20 (m, 4H), 1.44 (s, 9H). ES-LCMS: 332 (M+H).

Workup

  1. customThe dimethylformamide was removed
  2. additionether was added
  3. washThe ether layer was washed with brine (3×)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in 50 mL of methanol and hydrogenated with 2 g of 10% palladium on carbon under 45 psi of hydrogen gas at room temperature overnight
  7. customThe catalyst was removed by filtration
  8. concentrationthe filtrate was concentrated
  9. dissolutionThe residue was dissolved in 30 mL of dichloromethane
  10. stirringThe reaction mixture was stirred at room temperature overnight
  11. customAfter removal of solvent, purification by column chromatography with hexane:ethyl acetate (1:2) as eluant

Sources & evidence

ORD record
ord-86d9270a850543c4bbca32f82a207cd5
Source dataset
uspto-grants-2007_10
Patent number
US07288541B2

Reaction notes

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