3,3-Diphenyl-3,4,5,6-tetrahydropyridin-2-ol → HCID 67445694, compound

HRID 1667208Notes

Reaction equation

HRID 1667208 reaction equation
CC(C)([O-])C.[K+].[C:7]1([C:13]2([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:18][CH2:17][CH2:16][NH:15][C:14]2=[O:19])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Br[CH2:27][C:28]([N:30]([CH:41]1[CH2:46][CH2:45][N:44]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[CH2:43][CH2:42]1)[C:31]1[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][CH:32]=1)=[O:29]>O1CCCC1.[Cl-].[Na+].O>[O:19]=[C:14]1[C:13]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:18][CH2:17][CH2:16][N:15]1[CH2:27][C:28]([N:30]([CH:41]1[CH2:46][CH2:45][N:44]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[CH2:43][CH2:42]1)[C:31]1[CH:36]=[CH:35][C:34]([C:37]([F:38])([F:39])[F:40])=[CH:33][CH:32]=1)=[O:29]

Participants

6

Reactant 3

HCID 3211653,3-Diphenyl-3,4,5,6-tetrahydropyridin-2-olHCID 23665647Potassium tert-butoxideHCID 67445908tert-Butyl 4-[2-bromo-N-[4-(trifluoromethyl)phenyl]acetamido]piperidine-1-carboxylate

Product 1

HCID 67445694HCID 67445694, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of potassium tert-butoxide (1.0 M in tetrahydrofuran, 0.70 mL, 0.70 mmol) was added dropwise via syringe to a suspension of the product of Example 68C (147 mg, 0.587 mmol) in anhydrous tetrahydrofuran (5 mL) at ambient temperature. The reaction mixture was stirred for 45 minutes, and then a solution of the product of Example 166B (273 mg, 0.587 mmol) in 3 mL tetrahydrofuran was added. The reaction was allowed to proceed for 1 hour at ambient temperature, then poured into brine. The product was extracted with ethyl acetate and the combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by chromatography on silica gel (Analogix® Intelliflash™ 280; SF15-24 g column; 25%-75% ethyl acetate/hexanes, 0-15 minutes, 30 mL/minute) to afford the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.69 (d, J=8.3, 2H), 7.35 (d, J=8.2, 2H), 7.32-7.15 (m, 10H), 4.86-4.72 (m, 1H), 4.24-4.05 (m, 2H), 3.67 (bs, 2H), 3.45 (t, J=6.3, 2H), 2.80 (t, J=12.6, 2H), 2.67-2.55 (m, 2H), 1.90-1.73 (m, 4H), 1.39 (s, 9H), 1.29-1.11 (m, 2H); MS (DCI+) m/z 636 (M+H)+.

Workup

  1. waitto proceed for 1 hour at ambient temperature
  2. extractionThe product was extracted with ethyl acetate
  3. washthe combined organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by chromatography on silica gel (Analogix® Intelliflash™ 280; SF15-24 g column; 25%-75% ethyl acetate/hexanes, 0-15 minutes, 30 mL/minute)

Sources & evidence

ORD record
ord-74a7406a092f4c0aa25be85ca20e1bb9
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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