Triethylamine → HCID 86602052, compound

HRID 1295367Notes

Reaction equation

HRID 1295367 reaction equation
C(N(CC)CC)C.[F:8][C:9]([F:25])([F:24])[C:10]1[CH:11]=[C:12]([C@@H:20]([NH:22][CH3:23])[CH3:21])[CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=1.Cl[C:27](Cl)([O:29][C:30](=[O:36])OC(Cl)(Cl)Cl)Cl.[C:38]1([CH:44]2[NH:49][CH2:48][CH:47]3C2(CO)[CH2:46]3)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl.C(#N)C>[C:38]1([C@@H:44]2[NH:49][CH2:48][CH:47]3[C@:27]2([O:29][C:30](=[O:36])[N:22]([C@H:20]([C:12]2[CH:11]=[C:10]([C:9]([F:24])([F:25])[F:8])[CH:15]=[C:14]([C:16]([F:17])([F:18])[F:19])[CH:13]=2)[CH3:21])[CH3:23])[CH2:46]3)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 11608744(S)-N-Methyl-1-[3,5-bis(trifluoromethyl)phenyl]ethylamineHCID 58907340HCID 58907340, compound

Product 1

HCID 86602052HCID 86602052, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a round bottom flask was added methylene chloride (12 mL), triethylamine (0.55 mL, 3.9 mmol), and [(S)-1-(3,5-bis-trifluoromethyl-phenyl)-ethyl]-methyl-amine (0.35 g, 1.3 mmol). The mixture was cooled to 0° C. and triphosgene (0.15 g, 0.50 mmol) in methylene chloride (4 mL) was added dropwise. The clear solution was stirred for 16 hours at room temperature. To the reaction mixture was added (2-phenyl-3-aza-bicyclo[3.1.0]hex-1-yl)-methanol (0.25 g, 1.2 mmol), diisopropyl ethyl amine (0.41 mL, 2.4 mmol), and acetonitrile (10 mL). The reaction was heated to remove the methylene chloride and then refluxed for 1 hour. The solvent was removed at reduced pressure and the residue partitioned between 0.25N HCl and methylene chloride, the organic phase was washed with saturated sodium bicarbonate solution, brine, dried over sodium sulfate, filtered, and concentrated to a quantitative yield of oil. This material was flash chromatographed on silica using a gradient of 20 to 40% EtOAc/Hexanes and the first eluted (Rf=0.39 (50% EtOAc/hexanes) spot was rechromatographed using prep TLC eluting with 5% MeOH/CHCl3 to afford the title compound as a mixture of diasteomers (0.031 g, 5.5% yield) and as an oil.

Workup

  1. temperatureThe reaction was heated
  2. customto remove the methylene chloride
  3. temperaturerefluxed for 1 hour
  4. customThe solvent was removed at reduced pressure
  5. customthe residue partitioned between 0.25N HCl and methylene chloride
  6. washthe organic phase was washed with saturated sodium bicarbonate solution, brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered

Sources & evidence

ORD record
ord-c8201f0f28eb4523b4848641551424f1
Source dataset
uspto-grants-2007_07
Patent number
US07241798B2

Reaction notes

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