Methyl trifluoromethyl ketone → HCID 86707906, compound

HRID 877829Notes

Reaction equation

HRID 877829 reaction equation
F[C:2](F)(F)[C:3]([CH3:5])=[O:4].CC1[CH2:10][N:11]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:12]C=1.OOS([O-])=O.[K+].C(=O)(O)[O-].[Na+]>C(#N)C.C(N(CC(O)=O)CC(O)=O)CN(CC([O-])=O)CC([O-])=O.O.O.[Na+].[Na+]>[CH3:2][C:3]12[O:4][CH:5]1[CH2:10][N:11]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[CH2:12]2

Participants

7

Reactant 4

HCID 9871Methyl trifluoromethyl ketoneHCID 516892Sodium BicarbonateHCID 20090036HCID 20090036, compoundHCID 23707502Potassium hydroxy sulfite

Product 1

HCID 86707906HCID 86707906, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 44120005Edta disodiumCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A 0.004 M aqueous solution of EDTA disodium salt dihydrate (354 mL, 0.142 mmol) and 1,1,1-trifluoroacetone (49.6 mL, 567 mmol) was added sequentially to a solution of benzyl 3-methyl-2,5-dihydro-1H-pyrrole-1-carboxylate (15.4 g, 70.9 mmol) in acetonitrile (700 mL) at 0° C. A mixture of oxone (153 g, 248 mmol) and sodium bicarbonate (35.7 g, 425 mmol) was added in 5 portions over 1 h. After additions were complete, the mixture was stirred for another hour at 0° C. and filtered. The filtrate was extracted with dichloromethane (3×300 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated. Silica gel chromatography, eluting with 10-40% ethyl acetate in hexanes, gave benzyl 1-methyl-6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate (12.5 g, 76% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 7.73-7.30 (m, 5H), 5.21-4.94 (m, 2H), 4.33-4.05 (m, 1H), 3.93-3.70 (m, 2H), 3.56-3.13 (m, 2H), 1.58-1.44 (m, 3H).

Workup

  1. additionwas added in 5 portions over 1 h
  2. filtrationfiltered
  3. extractionThe filtrate was extracted with dichloromethane (3×300 mL)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. washSilica gel chromatography, eluting with 10-40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-b3c6847ae8db4c098d5fdedd8b007ed2
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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