Cornforth reagent → 2-[(3S)-12-[(4-[[(tert-butoxy)carbonyl](methyl)amino]cyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetic acid

HRID 1503904Notes

Reaction equation

HRID 1503904 reaction equation
[OH:1][CH2:2][CH2:3][C@@H:4]1[CH2:15][CH2:14][C:13]2[S:12][C:11]3[N:10]=[CH:9][N:8]=[C:7]([O:16][CH:17]4[CH2:22][CH2:21][CH:20]([N:23]([CH3:31])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:19][CH2:18]4)[C:6]=3[C:5]1=2.[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=[O:33].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>CN(C=O)C>[C:26]([O:25][C:24]([N:23]([CH3:31])[CH:20]1[CH2:19][CH2:18][CH:17]([O:16][C:7]2[C:6]3[C:5]4[C@H:4]([CH2:3][C:2]([OH:33])=[O:1])[CH2:15][CH2:14][C:13]=4[S:12][C:11]=3[N:10]=[CH:9][N:8]=2)[CH2:22][CH2:21]1)=[O:30])([CH3:28])([CH3:27])[CH3:29]

Participants

4

Reactant 2

HCID 2724130Cornforth reagentHCID 68115524tert-butyl N-(4-[[(3 S)-3-(2-hydroxyethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate

Product 1

HCID 681154802-[(3S)-12-[(4-[[(tert-butoxy)carbonyl](methyl)amino]cyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetic acidYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 22.3 (1.25 g, 2.79 mmol, 1.00 equiv) and dipyridinium dichromate (4 g, 10.64 mmol, 4.00 equiv) in 10 mL of DMF was stirred for 15 h at room temperature. The reaction was then quenched with water and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was loaded onto a silica gel column with ethyl acetate/petroleum ether (1:2 to 3:5) and purified to afford 2-[(3S)-12-[(4-[[(tert-butoxy)carbonyl](methyl)amino]cyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetic acid (22.4, 900 mg, 70%) as a colourless oil.

Workup

  1. customThe reaction was then quenched with water
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. custompurified

Sources & evidence

ORD record
ord-d039ad30ac364770963edf093d140cbf
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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