Methanol → HCID 59053668, compound

HRID 1748206Notes

Reaction equation

HRID 1748206 reaction equation
[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[O:15][C:16]([F:19])([F:18])[F:17])[C:5]=2[CH2:20][O:21][CH:22]2[CH2:28][CH:27]3[N:29]([C:30]4[S:31][C:32]5[CH:38]=[C:37](C(OCC)=O)[CH:36]=[CH:35][C:33]=5[N:34]=4)[CH:24]([CH2:25][CH2:26]3)[CH2:23]2)[CH2:3][CH2:2]1.C[Mg]Cl.[CH3:47]O.[CH2:49]1[CH2:53][O:52]CC1>C(OCC)(=O)C>[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[O:15][C:16]([F:19])([F:17])[F:18])[C:5]=2[CH2:20][O:21][CH:22]2[CH2:28][CH:27]3[N:29]([C:30]4[S:31][C:32]5[CH:38]=[C:37]([C:53]([OH:52])([CH3:49])[CH3:47])[CH:36]=[CH:35][C:33]=5[N:34]=4)[CH:24]([CH2:25][CH2:26]3)[CH2:23]2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 59053667HCID 59053667, compoundHCID 178418332HCID 178418332, compound

Product 1

HCID 59053668HCID 59053668, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

The ethyl ester Example 3-A, ethyl 2-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)benzo[d]thiazole-6-carboxylate (20 mg, 0.033 mmol) was dissolved in THF (1.0 mL), and at RT was charged with a solution of methyl magnesium chloride (0.4 mL, 3.0 M THF, 1.2 mmol) in a dropwise fashion over a few minutes slowly enough so as not to allow the internal temperature of the reaction to exceed 30° C. After 1 hr the reaction was cooled to 0° C. and treated with MeOH (3 mL) in a dropwise fashion (rapid evolution of gas, internal temperature did not exceed 10° C.). The reaction was allowed to warm on its own accord to RT and diluted with ethyl acetate (9 mL) and the cloudy suspension was washed with 2×1 mL of 1 N HCl. The organic extracts were dried in vacuo and the resulting residue was purified using mass-directed reverse phase HPLC using gradient of 30 to 90% acetonitrile/water with 0.05% TFA as modifier. The resulting product was cold vacuum concentrated and free based using an SPE polymer support cartridge and MeOH (2 mL) mobilizing solvent (product SPE PLHCO3 MP part no PL3540-C603). All resulting methanol effluent was concentrated to furnish the title compound as a white powder.

Workup

  1. customthe internal temperature of the reaction
  2. customto exceed 30° C
  3. customdid not exceed 10° C.
  4. temperatureto warm on its own accord to RT
  5. washthe cloudy suspension was washed with 2×1 mL of 1 N HCl
  6. customThe organic extracts were dried in vacuo
  7. customthe resulting residue was purified
  8. concentrationconcentrated
  9. concentrationAll resulting methanol effluent was concentrated

Sources & evidence

ORD record
ord-dc5685f23dc3424ca7a0362845ddb921
Source dataset
uspto-grants-2015_10
Patent number
US09150568B2

Reaction notes

Loading…