Trifluoroacetic acid → Ethyl 2-(3-((5-cyclopropyl-3-((trans)-2-(trifluoromethyl)cyclohexyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)benzo[d]thiazole-6-carboxylate

HRID 1748208Notes

Reaction equation

HRID 1748208 reaction equation
[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C@@H:9]3[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]3[C:15]([F:18])([F:17])[F:16])[C:5]=2[CH2:19][O:20][CH:21]2[CH2:27][CH:26]3[N:28](C(OC(C)(C)C)=O)[CH:23]([CH2:24][CH2:25]3)[CH2:22]2)[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O.CCN(C(C)C)C(C)C.Cl[C:53]1[S:54][C:55]2[CH:61]=[C:60]([C:62]([O:64][CH2:65][CH3:66])=[O:63])[CH:59]=[CH:58][C:56]=2[N:57]=1>ClCCl.O>[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C@@H:9]3[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]3[C:15]([F:18])([F:16])[F:17])[C:5]=2[CH2:19][O:20][CH:21]2[CH2:22][CH:23]3[N:28]([C:53]4[S:54][C:55]5[CH:61]=[C:60]([C:62]([O:64][CH2:65][CH3:66])=[O:63])[CH:59]=[CH:58][C:56]=5[N:57]=4)[CH:26]([CH2:25][CH2:24]3)[CH2:27]2)[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 12692400Ethyl 2-chloro-1,3-benzothiazole-6-carboxylateHCID 86704411Tert-butyl 3-((5-cyclopropyl-3-((trans)-2-(trifluoromethyl)cyclohexyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Product 1

HCID 59054384Ethyl 2-(3-((5-cyclopropyl-3-((trans)-2-(trifluoromethyl)cyclohexyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)benzo[d]thiazole-6-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl 3-((5-cyclopropyl-3-((trans)-2-(trifluoromethyl)cyclohexyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octane-8-carboxylate (67 mg, 0.13 mmol) in dichloromethane (1 mL) was treated with TFA (500 μL) and stirred for 1 hr at rt. The reaction was concentrated in vacuo and then diluted with NMP (1 mL) and then treated with Hunig's base (110 μL, 0.67 mmol) followed by ethyl 2-chlorobenzo[d]thiazole-6-carboxylate (33 mg, 0.13 mmol). After heating overnight at 120° C., the reaction was poured into water and extracted with EtOAc. The organic phase was collected, dried (MgSO4), filtered, and concentrated. The crude residue was purified by chromatography (SiO2, linear gradient, 0-60%, EtOAc in Hexanes) to give the title compound.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. additiondiluted with NMP (1 mL)
  3. temperatureAfter heating overnight at 120° C.
  4. extractionextracted with EtOAc
  5. customThe organic phase was collected
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by chromatography (SiO2, linear gradient, 0-60%, EtOAc in Hexanes)

Sources & evidence

ORD record
ord-3626bd9f09574dad84509714263e02e2
Source dataset
uspto-grants-2015_10
Patent number
US09150568B2

Reaction notes

Loading…