Methanol → HCID 56598014, compound

HRID 238567Notes

Reaction equation

HRID 238567 reaction equation
[Si](O[C@@:9]1([Cl:37])[C:16]([CH2:17][CH2:18][CH3:19])=[C:15]([NH:20][CH:21]([C:24]2[O:25][C:26]([C:29]3[CH:34]=[CH:33][C:32]([C:35]#[N:36])=[CH:31][CH:30]=3)=[N:27][N:28]=2)[CH2:22][CH3:23])[CH:14]=[CH:13][C@@H:10]1[C:11]#[N:12])(C(C)(C)C)(C)C.C[OH:39].[F-].[NH4+]>O.CCOC(C)=O.CC(OC)(C)C>[Cl:37][C:9]1[C:16]([CH2:17][CH2:18][CH3:19])=[C:15]([NH:20][C@@H:21]([C:24]2[O:25][C:26]([C:29]3[CH:30]=[CH:31][C:32]([C:35]#[N:36])=[CH:33][CH:34]=3)=[N:27][N:28]=2)[C@@H:22]([OH:39])[CH3:23])[CH:14]=[CH:13][C:10]=1[C:11]#[N:12]

Participants

7

Reactant 3

HCID 887MethanolHCID 25516Ammonium fluorideHCID 86660790HCID 86660790, compound

Product 1

HCID 56598014HCID 56598014, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

A 100 mL round bottom was charged with 4-((1R,2S)-2-(tert-butyldimethylsilyloxy)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)propylamino-2-chloro-3-propylbenzonitrile (intermediate 1119-D) (0.344 g, 0.64 mmole) and methanol (10 mL) at room temperature. Ammonium fluoride (0.119 g, 3.20 mmol) was then added in one portion and the reaction mixture was brought to reflux. The reaction stirred at reflux for 65 h before being cooled to room temperature. To the resulting reaction mixture was added water (50 mL), TBME (30 mL), EtOAc (50 mL) and more water (40 mL). The biphasic mixture was separated and the aqueous layer was extracted with EtOAc (50 mL). The organic extracts were then combined, washed with water (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to provide a brown solid. The brown solid was then purified by flash chromatography over silica gel [EtOAc-hexanes (50%:50%)→EtOAc-hexanes (100%:0%) as eluent] to provide the title compound with other minor impurities (200.7 mg, 74%). 1H NMR (400 MHz, CDCl3 δ in ppm): 8.07 (d, J=8.0 Hz, 2H), 7.77 (d, J=8.0 Hz, 2H), 7.34 (d, J=8.0 Hz, 1H), 6.60 (d, J=8.0 Hz, 1H), 5.45 (d, J=8.0 Hz, 1H), 4.80 (d, J=2.0, 8.0 Hz, 1H), 4.60 (m, 1H), 2.79 (t, J=8.0 Hz, 2H), 1.64 (sextet, J=8.0 Hz, 2H), 1.46 (d, J=4.0 Hz, 3H), 1.07 (t, J=8.0 Hz, 3H).

Workup

  1. temperatureto reflux
  2. temperatureat reflux for 65 h
  3. customTo the resulting reaction mixture
  4. customThe biphasic mixture was separated
  5. extractionthe aqueous layer was extracted with EtOAc (50 mL)
  6. washwashed with water (50 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto provide a brown solid
  11. customThe brown solid was then purified by flash chromatography over silica gel [EtOAc-hexanes (50%:50%)→EtOAc-hexanes (100%:0%) as eluent]

Sources & evidence

ORD record
ord-79adb8e9d8d048289d5a5e3873190b22
Source dataset
uspto-grants-2014_02
Patent number
US08642632B2

Reaction notes

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