Triethylamine → HCID 86706868, compound

HRID 717888Notes

Reaction equation

HRID 717888 reaction equation
ClC(OCC(C)C)=O.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([NH:22][C:23]2[CH:24]=[C:25]([CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[N:31]=2)[C:26](O)=[O:27])[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C(N(CC)CC)C.[BH4-].[Na+]>O1CCCC1.O>[OH:27][CH2:26][C:25]1[CH:29]=[C:30]([C:32]([F:35])([F:33])[F:34])[N:31]=[C:23]([NH:22][CH:19]2[CH2:20][CH2:21][N:16]([C:14]([O:13][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:15])[CH2:17][CH2:18]2)[CH:24]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 86706867HCID 86706867, compound

Product 1

HCID 86706868HCID 86706868, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Isobutyl chloroformate (1.1 mL, 8.6 mmol) was added to a solution of 2-{[1-(tert-butoxycarbonyl)piperidin-4-yl]amino}-6-(trifluoromethyl)isonicotinic acid (2.8 g, 7.2 mmol, from Step 2) and triethylamine (2.0 mL, 14 mmol) in tetrahydrofuran (30. mL) at 0° C. After stirring for 30 minutes, the reaction mixture was filtered through a short pad of celite into a flask containing a mixture of sodium tetrahydroborate (0.95 g, 25 mmol) in water (15 mL) at 0° C. The celite pad was rinsed with three portions of THF (3×30 mL) into the reaction flask. The reaction was allowed to warm to room temperature and stir for 1 hour. The reaction mixture was recooled in an ice bath and was quenched by the addition of saturated ammonium chloride solution. The product was extracted with a 150 mL portion of ethyl acetate. The organic layer was washed with water and brine, was dried over sodium sulfate, filtered and concentrated. Flash chromatography, using a 120 g silica gel cartridge and eluting with a gradient from 0-80% EtOAc in hexanes afforded product as a white solid (2.7 g, 100%). 1H NMR (400 MHz, CDCl3) δ 6.87 (s, 1H), 6.56 (s, 1H), 5.02-4.36 (m, 2H), 4.09-3.94 (m, 2H), 3.81 (dtt, J=14.2, 8.0, 3.9 Hz, 1H), 3.03-2.85 (m, 2H), 2.07-1.97 (m, 2H), 1.46 (s, 9H), 1.37 (qd, J=12.2, 3.8 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ −69.21 (s). LCMS (M+Na)+: 398.0.

Workup

  1. filtrationthe reaction mixture was filtered through a short pad of celite into a flask
  2. additioncontaining
  3. washThe celite pad was rinsed with three portions of THF (3×30 mL) into the reaction flask
  4. stirringstir for 1 hour
  5. customThe reaction mixture was recooled in an ice bath
  6. customwas quenched by the addition of saturated ammonium chloride solution
  7. extractionThe product was extracted with a 150 mL portion of ethyl acetate
  8. washThe organic layer was washed with water and brine
  9. dry with materialwas dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. washeluting with a gradient from 0-80% EtOAc in hexanes afforded product as a white solid (2.7 g, 100%)

Sources & evidence

ORD record
ord-c11aa1d75a464ceab2c827c1b8c26a5b
Source dataset
uspto-grants-2015_11
Patent number
US09193733B2

Reaction notes

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