Methanesulfonyl chloride → (2R,3R,4S)-5-azido-2-(tert-butoxycarbonylamino)-3-(tert-butyldimethylsilyloxy)-4-methylpentyl methanesulfonate

HRID 879152Notes

Reaction equation

HRID 879152 reaction equation
[N:1]([CH2:4][C@H:5]([CH3:26])[C@@H:6]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[C@H:7]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:8][OH:9])=[N+:2]=[N-:3].[CH3:27][S:28](Cl)(=[O:30])=[O:29]>N1C=CC=CC=1.CN(C1C=CN=CC=1)C.CCOCC.C(OCC)(=O)C>[CH3:27][S:28]([O:9][CH2:8][C@@H:7]([NH:10][C:11]([O:12][C:13]([CH3:16])([CH3:14])[CH3:15])=[O:17])[C@H:6]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:20])[CH3:21])[C@@H:5]([CH3:26])[CH2:4][N:1]=[N+:2]=[N-:3])(=[O:30])=[O:29]

Participants

7

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 86639730tert-butyl (2R,3R,4S)-5-azido-3-(tert-butyldimethylsilyloxy)-1-hydroxy-4-methylpentan-2-ylcarbamate

Product 1

HCID 59226467(2R,3R,4S)-5-azido-2-(tert-butoxycarbonylamino)-3-(tert-butyldimethylsilyloxy)-4-methylpentyl methanesulfonateYield 90%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl (2R,3R,4S)-5-azido-3-(tert-butyldimethylsilyloxy)-1-hydroxy-4-methylpentan-2-ylcarbamate (1.0 equiv.) in pyridine (0.2 M) was added MsCl (1.3 equiv.) followed by DMAP (catalytic amount) at 0° C. The mixture was stirred at that temperature for 1 hour. The solution was diluted with ether and ethyl acetate (4:1), washed with aq. NaHSO4, sat. NaHCO3, brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography eluting with ethyl acetate and hexanes (1:3) to give (2R,3R,4S)-5-azido-2-(tert-butoxycarbonylamino)-3-(tert-butyldimethylsilyloxy)-4-methylpentyl methanesulfonate as the major isomer (5:2) in 90% yield. LC/MS=367.3 (M+H-Boc), Rt=0.81 min (Frac 65%-95% method).

Workup

  1. washwashed with aq. NaHSO4, sat. NaHCO3, brine
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography
  6. washeluting with ethyl acetate and hexanes (1:3)

Sources & evidence

ORD record
ord-f6aaf26c7c3c441ba571e04714568bcd
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Reaction notes

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