Methanesulfonyl chloride → (1R,2R,4R,6S)-2-(tert-butoxycarbonylamino)-4-(3-(tert-butoxycarbonylamino)pyridin-4-yl)-6-methylcyclohexyl methanesulfonate

HRID 879179

Reaction equation

HRID 879179 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][C:14]=1[C@H:15]1[CH2:20][C@@H:19]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C@H:18]([OH:29])[C@@H:17]([CH3:30])[CH2:16]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:31][S:32](Cl)(=[O:34])=[O:33]>N1C=CC=CC=1>[CH3:31][S:32]([O:29][C@@H:18]1[C@@H:17]([CH3:30])[CH2:16][C@@H:15]([C:14]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:20][C@H:19]1[NH:21][C:22]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:28])(=[O:34])=[O:33]

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 86705222(+/-)-tert-butyl ((1R,2R,3S,5R)-5-(3-((tert-butoxycarbonyl)amino)pyridin-4-yl)-2-hydroxy-3-methylcyclohexyl)carbamate

Product 1

HCID 86705223(1R,2R,4R,6S)-2-(tert-butoxycarbonylamino)-4-(3-(tert-butoxycarbonylamino)pyridin-4-yl)-6-methylcyclohexyl methanesulfonateYield 59%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of (+/−)-tert-butyl ((1R,2R,3S,5R)-5-(3-((tert-butoxycarbonyl)amino)pyridin-4-yl)-2-hydroxy-3-methylcyclohexyl)carbamate (1.0 equiv.) in pyridine (0.17 M) was added MsCl (5.0 equiv.). The capped solution was stirred for 5 minutes and then the homogeneous solution was left standing at rt for 16 hrs. The volatiles were removed in vacuo and the residue was partitioned between EtOAc and H2O. The organic layer was washed with H2O, 10% CuSO4, H2O, Na2CO3(sat.), NaCl(sat.), dried over MgSO4, filtered, concentrated and purified by ISCO SiO2 chromatography to yield (+/−)-(1R,2R,4R,6S)-2-(tert-butoxycarbonylamino)-4-(3-(tert-butoxycarbonylamino)pyridin-4-yl)-6-methylcyclohexyl methanesulfonate in 59% yield. LC/MS (m/z)=500.3 (MH+), Rt=0.74 min.

Workup

  1. waitthe homogeneous solution was left
  2. waitstanding at rt for 16 hrs
  3. customThe volatiles were removed in vacuo
  4. customthe residue was partitioned between EtOAc and H2O
  5. washThe organic layer was washed with H2O, 10% CuSO4, H2O, Na2CO3(sat.), NaCl(sat.)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by ISCO SiO2 chromatography

Sources & evidence

ORD record
ord-9afb276e19674b7ea200796c242a7494
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Linked notes

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