Citric Acid → 4-(3-(Trifluoromethyl)-3H-diazirin-3-yl)benzyl Alcohol

HRID 73140Notes

Reaction equation

HRID 73140 reaction equation
II.C([Si](C)(C)[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2([C:19]([F:22])([F:21])[F:20])[NH:18][NH:17]2)=[CH:12][CH:11]=1)(C)(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.Cl.O1CCOCC1>CO.CCN(CC)CC>[F:22][C:19]([F:20])([F:21])[C:16]1([C:13]2[CH:12]=[CH:11][C:10]([CH2:9][OH:8])=[CH:15][CH:14]=2)[N:17]=[N:18]1

Participants

8

Reactant 5

HCID 311Citric AcidHCID 313Hydrochloric AcidHCID 807IodineHCID 312751,4-DioxaneHCID 130632033-(4-(((tert-Butyl(dimethyl)silyl)oxy)methyl)phenyl)-3-(trifluoromethyl)diaziridine

Product 1

HCID 113679054-(3-(Trifluoromethyl)-3H-diazirin-3-yl)benzyl AlcoholYield 78%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8471TriethylamineSolvent

Procedure

I2 (1.14 g, 4.5 mmol) was added to a MeOH (4 mL) solution of Et3N (1.2 mL) and 3-(4-((tert.-butyldimethylsilyloxy)methyl)phenyl)-3-(trifluoromethyl)-diaziridine (1.65 g, 5.00 mmol). The solution was stirred at rt (3 h). Aqueous citric acid 10% (50 mL) and NaS2O3 were added. The organic layer was extracted 3 times with ether (3×30 mL). The organic layers were combined, dried and concentrated in vacuum to obtain a yellow oil; 1H NMR (CDCl3): δ 0.09 (s, (CH3)2Si), 0.94 (s, CH3)3C), 4.74 (s, CH2), 7.15 (d, J=8.0 Hz, 2 C6H4), 7.35 (d, J=8.0 Hz, 2 C6H4). HCl in dioxane (4 M, 5 mL, 20 mmol) was added to a MeOH (10 mL) solution of the yellow residue. The solution was stirred at rt (3 h) and the volatiles were evaporated. The residue was purified by silica gel flash chromatography to obtain 840 mg (78%) of a yellow liquid: Rf=0.19 (1/9 EtOAc/hexanes); 1H NMR (CDCl3): δ 1.95-2.05 (br, OH), 4.70 (s, CH2), 7.18 (d, J=8.4 Hz, 2 C6H4), 7.38 (d, J=8.4 Hz, 2C6H4); 13C NMR (CDCl3): δ 28.3 (q, J=40.4 Hz, C diazirine), 64.4 (CH2O), 122.1 (q, J=273.0 Hz, CF3), 126.7 (C6H2), 127.1 (C6H2), 128.3 (C6H2), 142.5 (C6H2).

Workup

  1. extractionThe organic layer was extracted 3 times with ether (3×30 mL)
  2. customdried
  3. concentrationconcentrated in vacuum
  4. customto obtain a yellow oil
  5. stirringThe solution was stirred at rt (3 h)
  6. customthe volatiles were evaporated
  7. customThe residue was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-fdf169803df444c3955b08a67e984b8c
Source dataset
uspto-grants-2014_09
Patent number
US08829033B2

Reaction notes

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