Cornforth reagent → 2-[(3R)-12-[(4-[[(tert-butoxy)carbonyl](ethyl)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 1503956Notes

Reaction equation

HRID 1503956 reaction equation
[CH2:1]([N:3]([CH:11]1[CH2:16][CH2:15][CH:14]([O:17][C:18]2[C:29]3[C:28]4[C@@H:27]([CH2:30][CH2:31][OH:32])[CH2:26][CH2:25][C:24]=4[S:23][C:22]=3[N:21]=[CH:20][N:19]=2)[CH2:13][CH2:12]1)[C:4](=[O:10])[O:5][C:6]([CH3:9])([CH3:8])[CH3:7])[CH3:2].C1C=C[NH+]=CC=1.C1C=C[NH+]=CC=1.[O-:45][Cr](O[Cr]([O-])(=O)=O)(=O)=O>CN(C=O)C.O>[C:6]([O:5][C:4]([N:3]([CH2:1][CH3:2])[CH:11]1[CH2:12][CH2:13][CH:14]([O:17][C:18]2[C:29]3[C:28]4[C@@H:27]([CH2:30][C:31]([OH:45])=[O:32])[CH2:26][CH2:25][C:24]=4[S:23][C:22]=3[N:21]=[CH:20][N:19]=2)[CH2:15][CH2:16]1)=[O:10])([CH3:8])([CH3:7])[CH3:9]

Participants

5

Reactant 2

HCID 2724130Cornforth reagentHCID 68110398tert-butyl N-ethyl-N-(4-[[(3R)-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)carbamate

Product 1

HCID 681155382-[(3R)-12-[(4-[[(tert-butoxy)carbonyl](ethyl)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 67.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of tert-butyl N-ethyl-N-(4-[[(3R)-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)carbamate (450 mg, 0.97 mmol, 1.00 equiv) and PDC (1791 mg, 4.76 mmol, 4.88 equiv) in 5 mL of DMF was stirred for 14 hrs at 25° C. After completion, the resulting solution was diluted with water and extracted with 3×50 mL of ethyl acetate. The combined organic layers were washed with 3×20 mL of brine, dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (2:1) to give 310 mg (67%) of 2-[(3R)-12-[(4-[[(tert-butoxy)carbonyl](ethyl)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 as a colorless oil. MS (ES): m/z 476 [M+H]+.

Workup

  1. extractionextracted with 3×50 mL of ethyl acetate
  2. washThe combined organic layers were washed with 3×20 mL of brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-b7c9830ccc524c699155316fb4130d0c
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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