Trifluoroacetic acid → HCID 66935317, compound

HRID 1798835Notes

Reaction equation

HRID 1798835 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[C:27]1[O:28][C:29]([CH3:32])=[N:30][N:31]=1)[O:5][CH2:6][CH2:7][C@H:8]1[CH2:10][C@H:9]1[CH:11]1[CH2:16][CH2:15][N:14]([C:17](OC(C)(C)C)=O)[CH2:13][CH2:12]1.C(O)(C(F)(F)F)=O.ClC1[N:46]=[CH:45][C:44]([CH3:47])=[CH:43][N:42]=1.C1CCN2C(=NCCC2)CC1>ClCCl.O.CCOC(C)=O>[CH3:47][C:44]1[CH:43]=[N:42][C:17]([N:14]2[CH2:13][CH2:12][CH:11]([C@@H:9]3[CH2:10][C@@H:8]3[CH2:7][CH2:6][O:5][C:4]3[CH:24]=[CH:25][C:26]([C:27]4[O:28][C:29]([CH3:32])=[N:30][N:31]=4)=[C:2]([F:1])[CH:3]=3)[CH2:16][CH2:15]2)=[N:46][CH:45]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 5817192-Chloro-5-methylpyrimidineHCID 123588455HCID 123588455, compound

Product 1

HCID 66935317HCID 66935317, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

rac-cis-tert-Butyl 4-(2-{2-[3-fluoro-4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy]ethyl}cyclopropyl)piperidine-1-carboxylate from step 1 of this example (40 mg, 0.09 mmol) was dissolved in 0.5 mL dichloromethane. TFA (0.5 mL) was carefully added. The mixture was stirred at room temperature for 20 min, upon which the volatile TFA was removed in vacuo and further dried i. vac. for 2 hours. The residue was redissolved in 1 mL NMP. 2-Chloro-5-methylpyrimidine (23 mg, 0.18 mmol) and DBU (0.135 mL, 0.9 mmol) were sequentially added. The mixture was heated at 90° C. for 1.5 hours before cooled back to room temperature. The reaction was then diluted with 2 mL water and 0.5 mL EtOAc. The aqueous phase was further extracted twice with ethyl acetate. The combined organic layers were washed with water and brine, then concentrated and purified by column chromatography through a 12 gram biotage silica gel cartridge eluting with 20% ethyl acetate/hexanes to give the product as white-solid. LRMS talc: 437.2; obs: 438.7 (M+1). Compounds Reported in Table 2 are Prepared by a General Procedure Analogous to that Described in Example 84 Above.

Workup

  1. customwas removed in vacuo and further dried i
  2. dissolutionThe residue was redissolved in 1 mL NMP
  3. temperaturebefore cooled back to room temperature
  4. extractionThe aqueous phase was further extracted twice with ethyl acetate
  5. washThe combined organic layers were washed with water and brine
  6. concentrationconcentrated
  7. custompurified by column chromatography through a 12 gram biotage silica gel cartridge
  8. washeluting with 20% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-1f0f61c6b1254d47b803684dc3ef1a5b
Source dataset
uspto-grants-2013_01
Patent number
US08343990B2

Reaction notes

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