Ethyl Acetate → HCID 178442397, compound

HRID 1046401Notes

Reaction equation

HRID 1046401 reaction equation
[CH3:1][C:2]([CH3:31])([CH3:30])[C:3]#[C:4][C:5]1[S:9][C:8]([C:10]([OH:12])=[O:11])=[C:7]([N:13]([C@H:23]2[CH2:28][CH2:27][C@H:26]([OH:29])[CH2:25][CH2:24]2)[C:14]([C@H:16]2[CH2:21][CH2:20][C@H:19]([CH3:22])[CH2:18][CH2:17]2)=[O:15])[CH:6]=1.F[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=1.[H-].[Na+].C(OCC)(=O)C>CN(C=O)C>[CH3:31][C:2]([CH3:30])([CH3:1])[C:3]#[C:4][C:5]1[S:9][C:8]([C:10]([OH:12])=[O:11])=[C:7]([N:13]([C:14]([C@H:16]2[CH2:21][CH2:20][C@H:19]([CH3:22])[CH2:18][CH2:17]2)=[O:15])[C@H:23]2[CH2:28][CH2:27][C@H:26]([O:29][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=3)[CH2:25][CH2:24]2)[CH:6]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 97462-FluoropyridineHCID 24758Sodium hydrideHCID 178442400HCID 178442400, compound

Product 1

HCID 178442397HCID 178442397, compoundYield 71.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-(3,3-Dimethyl-but-1-ynyl)-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid (78 mg, 0.175 mmol) and 2-fluoro-pyridine (145 μL, 1.68 mmol) in DMF (0.6 mL) was treated with sodium hydride (67 mg, 1.68 mmol, 60% oil dispersion) in two or three portions. The mixture was stirred until the bubbling slowed, and was sealed and heated by microwave at 100 deg C. for 30 min. After cooling, ethyl acetate (2-3 mL) was added and the mixture was carefully quenched with citric acid (10% aqueous solution, 2-3 mL). Water was added and the mixture was extracted with ethyl acetate (2×30 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by HPLC (Gemini column, 35% acetonitrile:water, 2 min, 35-50% acetonitrile:water, 2 min, 50-95% acetonitrile:water 13 min, both solvents containing 0.1% trifluoroacetic acid). This resulted in 65 mg (58% yield) of the title compound as a white powder (TFA salt): MS (m/z): 520.9 [M−H]−; HPLC retention time: 4.61 min (2-98% acetonitrile:water with 0.05% trifluoroacetic acid).

Workup

  1. customwas sealed
  2. temperatureheated by microwave at 100 deg C
  3. temperatureAfter cooling
  4. customthe mixture was carefully quenched with citric acid (10% aqueous solution, 2-3 mL)
  5. additionWater was added
  6. extractionthe mixture was extracted with ethyl acetate (2×30 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by HPLC (Gemini column, 35% acetonitrile
  11. additionwater, 2 min, 35-50% acetonitrile:water, 2 min, 50-95% acetonitrile:water 13 min, both solvents containing 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-8e162c06913c4a9296625cb1a23e4394
Source dataset
uspto-grants-2013_10
Patent number
US08569302B2

Reaction notes

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