Tetrahydrofuran → HCID 86666505, compound

HRID 1426343Notes

Reaction equation

HRID 1426343 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[H-].[Na+].Cl[C:18]1[CH:19]=[C:20]([CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[N:25]=1)[C:21]#[N:22].[O:30]1CCCC1>O>[NH2:22][C:21]([C:20]1[CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[N:25]=[C:18]([O:1][CH:2]2[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]2)[CH:19]=1)=[O:30]

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 534076042-Chloro-6-(trifluoromethyl)pyridine-4-carbonitrile

Product 1

HCID 86666505HCID 86666505, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Tert-butyl 4-hydroxypiperidine-1-carboxylate (0.37 g, 1.8 mmol, Aldrich) was added to sodium hydride (74 mg, 1.8 mmol, 60% in mineral oil) in tetrahydrofuran (2.1 mL). After stirring for 45 minutes, 2-chloro-6-(trifluoromethyl)isonicotinonitrile (0.24 g, 0.93 mmol, from Step A) in tetrahydrofuran (1.3 mL) was introduced. After stirring overnight, the mixture was diluted with water and extracted with EtOAc. The combined extracts were washed with water, brine, dried over sodium sulfate, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-40% EtOAc in hexanes afforded product (0.20 g, 44%). 1H NMR (300 MHz, CDCl3) δ 7.58 (d, J=1.2 Hz, 1H), 7.23 (dd, J=1.3, 0.6 Hz, 1H), 6.15 (s, 1H), 5.75 (s, 1H), 5.30 (tt, J=1.1, 3.8 Hz, 1H), 3.95-3.62 (m, 4H), 3.33 (ddd, J=13.5, 8.4, 3.7 Hz, 2H), 3.02 (ddd, J=13.3, 9.8, 3.4 Hz, 2H), 1.58 (s, 9H); 19F NMR (282 MHz, CDCl3) 5-68.97 (s); LCMS (M+Na)+: 412.0.

Workup

  1. stirringAfter stirring overnight
  2. extractionextracted with EtOAc
  3. washThe combined extracts were washed with water, brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washFlash chromatography, eluting with a gradient from 0-40% EtOAc in hexanes afforded product (0.20 g, 44%)

Sources & evidence

ORD record
ord-8d0011cfde1d4c799c1089afbb32815f
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

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