4-Methoxybenzenesulfonyl chloride → HCID 5279194, compound

HRID 29211Notes

Reaction equation

HRID 29211 reaction equation
[CH2:1]([C@H:8]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[C@H:9]([OH:18])[CH2:10][NH:11][O:12][CH:13]([CH2:16][CH3:17])[CH2:14][CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:27][O:28][C:29]1[CH:34]=[CH:33][C:32]([S:35](Cl)(=[O:37])=[O:36])=[CH:31][CH:30]=1.C(N(C(C)C)CC)(C)C>O1CCCC1.CN(C)C1C=CN=CC=1>[CH2:1]([C@H:8]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:24])([CH3:23])[CH3:25])[C@H:9]([OH:18])[CH2:10][N:11]([O:12][CH:13]([CH2:14][CH3:15])[CH2:16][CH3:17])[S:35]([C:32]1[CH:31]=[CH:30][C:29]([O:28][CH3:27])=[CH:34][CH:33]=1)(=[O:37])=[O:36])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 74014-Methoxybenzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 57042275tert-butyl(1S,2R)-1-benzyl-3-[(1-ethylpropoxy)amino]-2-hydroxypropylcarbamate

Product 1

HCID 5279194HCID 5279194, compoundYield 70.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of tert-butyl (1S,2R)-1-benzyl-3-[(1-ethylpropoxy)amino]-2-hydroxypropylcarbamate (100 mg, 0.273 mmol), 4-methoxyphenylsulphonyl chloride (57 mg, 0.273 mmol), and diisoproylethylamine (0.0476 mL, 0.273 mmol) in anhydrous tetrahydrofuran (2 mL) was stirred under Argon for 16 hours at ambient temperature. A catalytic quantity of 4-dimethylaminopyridine (˜1 mg) was added and the reaction was heated at reflux for approximately two hours. After cooling, the reaction was evaporated in vacuo and the residue was dissolved in ethyl acetate. The solution was washed with aqueous potassium carbonate (5% w/v), aqueous hydrochloric acid (1N) and brine. The organic layer was then dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The residue was purified on a preparative TLC plate (20×20 cm, 500 NM) eluting with 95:5 methylene chloride:methanol. The product band was removed, eluted with 4:1 methylene chloride:methanol, filtered, and evaporated in vacuo. The residue was purified again on a preparative TLC plate (20×20 cm, 500 μM) eluting with 95:5 methylene chloride:ethyl acetate. The product band was removed, eluted with 4:1 methylene chloride:methanol, filtered, and evaporated in vacuo to provide tert-butyl (1S,2R)-1-benzyl-3-{(1-ethylpropoxy)[(4-methoxyphenyl)sulfonyl]amino}-2-hydroxypropylcarbamate (103 mg, 70%) as a foam. H1-NMR (chloroform-D3): 0.95 (m, 6H), 1.38 (s, 9H), 1.64 (m, 4H), 3.01 (m, 5H), 3.83 (m, 2H), 3.93 (s, 3H), 4.20 (m, 1H), 4.61 (m, 1H), 7.03 (d, 2H), 7.29 (m, 5H), 7.80 (d, 2H). MS(ESI): 559(M+Na).

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux for approximately two hours
  3. temperatureAfter cooling
  4. customthe reaction was evaporated in vacuo
  5. dissolutionthe residue was dissolved in ethyl acetate
  6. washThe solution was washed with aqueous potassium carbonate (5% w/v), aqueous hydrochloric acid (1N) and brine
  7. dry with materialThe organic layer was then dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe residue was purified on a preparative TLC plate (20×20 cm, 500 NM)
  11. washeluting with 95:5 methylene chloride
  12. customThe product band was removed
  13. washeluted with 4:1 methylene chloride
  14. filtrationmethanol, filtered
  15. customevaporated in vacuo
  16. customThe residue was purified again on a preparative TLC plate (20×20 cm, 500 μM)
  17. washeluting with 95:5 methylene chloride
  18. customThe product band was removed
  19. washeluted with 4:1 methylene chloride
  20. filtrationmethanol, filtered
  21. customevaporated in vacuo

Sources & evidence

ORD record
ord-77a4062e9fb24712a82ba81a68fb52e9
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Reaction notes

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