Triacetoxyperiodinane → HCID 57955225, compound

HRID 73697Notes

Reaction equation

HRID 73697 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[NH2:6][C:7]1[C:12]2=[C:13]([C:25]3[CH:30]=[CH:29][C:28]([NH:31][C:32]([NH:34][C:35]4[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[CH:37][N:36]=4)=[O:33])=[CH:27][CH:26]=3)[C:14]([CH:23]=[O:24])=[C:15]([CH2:16][N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[N:11]2[N:10]=[CH:9][N:8]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C1COCC1.CCOC(C)=O>[NH2:6][C:7]1[C:12]2=[C:13]([C:25]3[CH:26]=[CH:27][C:28]([NH:31][C:32]([NH:34][C:35]4[CH:40]=[C:39]([C:41]([F:43])([F:44])[F:42])[CH:38]=[CH:37][N:36]=4)=[O:33])=[CH:29][CH:30]=3)[C:14]([C:23]([CH:1]3[CH2:3][CH2:2]3)=[O:24])=[C:15]([CH2:16][N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[N:11]2[N:10]=[CH:9][N:8]=1

Participants

6

Reactant 3

HCID 159087TriacetoxyperiodinaneHCID 57955235HCID 57955235, compoundHCID 178418630HCID 178418630, compound

Product 1

HCID 57955225HCID 57955225, compoundYield 12.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Cyclopropyl magnesium bromide (7.40 mL, 3.70 mmol, 0.5 M in diethyl ether) was added dropwise to a stirring solution of Example 85 (200 mg, 0.37 mmol) in THF (10 mL). This was allowed to stir until the reaction was complete by HPLC (1 hour). Additional amounts of the grinard reagent were added as needed. The reaction was quenched with methanol and was worked up by adding 1 volume of saturated NH4Cl solution and 5 volumes of EtOAc. The organic layer was washed 2× with NH4Cl and 1× with sodium carbonate soln. The organic layer was dried over Na2SO4 and concentrated. The crude intermediate was dissolved in DMSO (3 nth) and treated with Dess-Martin periodinane (174.7 mg, 0.412 mmol). The reaction was allowed to stir until the reaction was complete by HPLC (2 hours). The reaction was diluted with EtOAc (200 mL) and washed 2× with both saturated NaHCO3 and 2M sodium thiosulfate solution. The organic layer was dried over Na2SO4 and concentrated to give a crude solid which was purified by HPLC (10-70% ACN/H2O) to give 26.3 mg of the above compound (0.04 mmol, 12.3% yield). 1H-NMR (DMSO-d6). δ 9.98 (s, 1H), 9.82 (s, 1H), 8.60 (d, J=5.4 Hz, 1H), 8.11 (s, 1H), 8.03 (s, 1H), 7.69 (d, J=8.4 Hz, 2H), 7.45-7.41 (m, 3H), 4.08 (s, 2H), 3.55-3.52 (m, 4H), 2.46-2.43 (m, 4 H), 2.07-1.97 (m, 1H), 0.95-0.91 (m, 2H), 0.74-0.69 (m, 2H). MS [M+H]+=581; LCMS RT=2.68 min.

Workup

  1. customwas complete by HPLC (1 hour)
  2. additionAdditional amounts of the grinard reagent were added
  3. customThe reaction was quenched with methanol
  4. additionby adding 1 volume of saturated NH4Cl solution and 5 volumes of EtOAc
  5. washThe organic layer was washed 2× with NH4Cl and 1× with sodium carbonate soln
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated
  8. dissolutionThe crude intermediate was dissolved in DMSO (3 nth)
  9. stirringto stir until the reaction
  10. customwas complete by HPLC (2 hours)
  11. washwashed 2× with both saturated NaHCO3 and 2M sodium thiosulfate solution
  12. dry with materialThe organic layer was dried over Na2SO4
  13. concentrationconcentrated
  14. customto give a crude solid which
  15. customwas purified by HPLC (10-70% ACN/H2O)

Sources & evidence

ORD record
ord-80d915d617f44f4bb171e464c3559df4
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Reaction notes

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