2,6-Lutidine → HCID 68678151, compound

HRID 1992205Notes

Reaction equation

HRID 1992205 reaction equation
O[CH:2]([CH3:13])[C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.N1C(C)=CC=CC=1C.C(N(C(C)C)CC)(C)C.Cl.Cl.[F:48][C:49]1[CH:50]=[C:51]([C:55]2([CH2:61][CH2:62][N:63]3[C@H:68]4[CH2:69][CH2:70][C@@H:64]3[CH2:65][CH:66]([N:71]3[C:75]5[CH:76]=[CH:77][CH:78]=[CH:79][C:74]=5[N:73]=[C:72]3[CH3:80])[CH2:67]4)[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]2)[CH:52]=[CH:53][CH:54]=1>C(Cl)Cl>[F:48][C:49]1[CH:50]=[C:51]([C:55]2([CH2:61][CH2:62][N:63]3[C@H:68]4[CH2:69][CH2:70][C@@H:64]3[CH2:65][CH:66]([N:71]3[C:75]5[CH:76]=[CH:77][CH:78]=[CH:79][C:74]=5[N:73]=[C:72]3[CH3:80])[CH2:67]4)[CH2:56][CH2:57][N:58]([CH:2]([CH3:13])[C:3]([O:5][CH2:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)=[O:4])[CH2:59][CH2:60]2)[CH:52]=[CH:53][CH:54]=1

Participants

7

Reactant 5

HCID 79372,6-LutidineHCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 98054Benzyl lactateHCID 68675921HCID 68675921, compound

Product 1

HCID 68678151HCID 68678151, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a −78° C. solution of benzyl 2-hydroxypropanoate (250 mg, 1.39 mmol) and 4A molecular sieves in 2 mL CH2Cl2 was added trifluoromethanesulfonic anhydride (0.33 mL, 1.97 mmol). After stirring for 10 min at this temperature, 2,6-lutidine (0.31 mL, 2.62 mmol) was added. After 15 min, diisopropylethylamine (0.46 mL, 2.62 mmol) was added and after another 15 min, a solution of 1-((1R,5S)-8-{2-[4-(3-fluorophenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole dihydrochloride (400 mg, 0.66 mmol) in 3 mL CH2Cl2 was added. The reaction mixture was stirred at −78° C., then allowed to warm to room temperature overnight, washed with saturated aqueous NaHCO3, and purified by chromatography (3% (2M NH3/MeOH) in CHCl3) to provide benzyl 2-(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-1-yl)propanoate (146 mg, 37%) as a solid. 1H NMR (400 MHz, CDCl3), δ 7.68 (m, 1H), 7.37-7.26 (m, 7H), 7.22-7.13 (m, 2H), 7.08 (m, 1H), 6.98 (m, 1H), 6.92 (m, 1H), 5.09 (s, 2H), 4.62 (m, 1H), 3.39-3.17 (m, 2H), 2.89-1.26 (m, 27H); ESI-MS 609 (M+H).

Workup

  1. additionwas added
  2. temperatureto warm to room temperature overnight
  3. washwashed with saturated aqueous NaHCO3
  4. custompurified by chromatography (3% (2M NH3/MeOH) in CHCl3)

Sources & evidence

ORD record
ord-b128f13c4afe4c54b1d8969fa94a306b
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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