Triethylamine → HCID 86602061, compound

HRID 1295378Notes

Reaction equation

HRID 1295378 reaction equation
C(N(CC)CC)C.[F:8][C:9]([F:25])([F:24])[C:10]1[CH:11]=[C:12]([CH:20]([NH:22][CH3:23])[CH3:21])[CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=1.ClC(Cl)(O[C:30](=[O:36])OC(Cl)(Cl)Cl)Cl.[C:38]([O:42][C:43](=[O:57])[NH:44][C@@:45]12[CH2:50][CH:49]1[CH2:48][NH:47][C@H:46]2[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)([CH3:41])([CH3:40])[CH3:39].C(N(C(C)C)CC)(C)C>C(Cl)Cl.C(#N)C>[C:38]([O:42][C:43](=[O:57])[NH:44][C@@:45]12[CH2:50][CH:49]1[CH2:48][N:47]([C:30](=[O:36])[N:22]([C@H:20]([C:12]1[CH:13]=[C:14]([C:16]([F:17])([F:18])[F:19])[CH:15]=[C:10]([C:9]([F:8])([F:24])[F:25])[CH:11]=1)[CH3:21])[CH3:23])[C@H:46]2[C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1)([CH3:41])([CH3:39])[CH3:40]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 220173563,5-Bis(trifluoromethyl)-alpha,N-dimethylbenzylamineHCID 69336084HCID 69336084, compound

Product 1

HCID 86602061HCID 86602061, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a round bottom flask was added methylene chloride (8 mL), triethylamine (0.87 mL, 6.3 mmol), and [(SR)-1-(3,5-bis-trifluoromethyl-phenyl)-ethyl]-methyl-amine (0.49 g, 1.6 mmol. The mixture was cooled to 0° C. and triphosgene (0.18 g, 0.61 mmol) in methylene chloride (3 mL) was added dropwise. The clear solution was stirred for 16 hours at room temperature. To the reaction mixture was added racemic Intermediate 48, one enantiomer being ((1S,2S)-2-phenyl-3-aza-bicyclo[3.1.0]hex-1-yl)-carbamic acid tert-butyl ester (0.40 g, 1.5 mmol), diisopropyl ethyl amine (0.25 mL, 1.5 mmol), and acetonitrile (8 mL). The reaction was heated to remove the methylene chloride and then refluxed for 2 hours. The solvent was removed at reduced pressure and the residue was partitioned between saturated citric acid solution and methylene chloride. The organic phase was washed with saturated sodium bicarbonate solution, brine, dried over sodium sulfate, filtered, and concentrated to give the title compounds as a foam (0.84 g, quantitative yield).

Workup

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

Sources & evidence

ORD record
ord-ee0fdaa97fef495bbf2e93c8464d91bf
Source dataset
uspto-grants-2007_07
Patent number
US07241798B2

Reaction notes

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