Trifluoroacetic acid → HCID 69018507, compound

HRID 1436522Notes

Reaction equation

HRID 1436522 reaction equation
[CH3:1][C@H:2]([NH2:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:10]([C:12](=O)[C:13]([O-:15])=[O:14])[CH3:11].F[C:18](F)(F)[C:19](O)=O.B(F)(F)F.CCOCC.[CH3:33][O:34][CH2:35][CH:36]1C=C[CH:38]=[CH:37]1.C1([Na])C=CC=C1.COCCl>ClCCl.O1CCCC1>[CH2:18]([O:15][C:13]([CH:12]1[CH:10]2[CH:36]([CH2:35][O:34][CH3:33])[CH:37]([CH:38]=[CH:11]2)[N:9]1[CH:2]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)[CH3:1])=[O:14])[CH3:19]

Participants

10

Reactant 7

HCID 6422Trifluoroacetic acidHCID 7864Chloromethyl Methyl EtherHCID 8000Boron trifluoride etherateHCID 758181-Phenethylamine, (-)-HCID 35932772-KetobutyrateHCID 125472885-(Methoxymethyl)cyclopenta-1,3-dieneHCID 178507085HCID 178507085, compound

Product 1

HCID 69018507HCID 69018507, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Add molecular sieves (3 Å, 12.0 g), (S)-(−)-α-methylbenzylamine (6.4 mL, 50.0 mmol) to a solution of ethylglyoxalate (10.3 mL, 50.0 mmol) in dichloromethane (200 mL) cooled in an ice bath. Stir the mixture at 0° C. for 2 h, and then cool to −78° C. Add trifluoroacetic acid (4.10 mL, 55.0 mmol), boron trifluoride etherate (6.90 mL, 55.0 mmol), and 5-methoxymethyl-1,3-cyclopentadiene (60.0 mmol, prepared in situ by adding cyclopentadienylsodium (2.0 M in THF, 30.0 mL, 60.0 mmol) to a solution of chloromethyl methyl ether (5.70 mL, 75.0 mmol) in tetrahydrofuran (30 mL) at −55° C.) with a 5 min interval between each addition. Stir for 2 h at −78° C. and refrigerate (−20° C.) overnight. Quench the reaction with saturated aqueous sodium bicarbonate solution (200 mL) and stir the mixture vigorously for 15 min. Separate the layers, dry the organic layer (magnesium sulfate), concentrate, and purify (silica gel chromatography 10:90 to 30:70 ethyl acetate:hexanes) to give the title compound (3.95 g, 25%).

Workup

  1. temperaturecooled in an ice bath
  2. temperaturecool to −78° C
  3. additionbetween each addition
  4. stirringStir for 2 h at −78° C.
  5. customrefrigerate (−20° C.) overnight
  6. customQuench
  7. customthe reaction with saturated aqueous sodium bicarbonate solution (200 mL)
  8. stirringstir the mixture vigorously for 15 min
  9. customSeparate the layers
  10. dry with materialdry the organic layer (magnesium sulfate)
  11. concentrationconcentrate
  12. custompurify (silica gel chromatography 10:90 to 30:70 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-c4c69a0d9d3344e087f38984250ab016
Source dataset
uspto-grants-2009_11
Patent number
US07618978B2

Reaction notes

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