tert-butyl 4-(4-(benzyloxy)-phenyl)-5-fluoro-5,6-dihydropyridine-1(2H)-carboxylate → cis-Tert-butyl 4-(4-(benzyloxy)phenyl)-3-fluoropiperidine-1-carboxylate

HRID 1507265Notes

Reaction equation

HRID 1507265 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]([F:21])[CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17][CH:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(OCC)(=O)C.[Pd]>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C@H:15]2[CH2:16][CH2:17][N:18]([C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])[CH2:19][C@H:20]2[F:21])=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 1

HCID 118207423tert-butyl 4-(4-(benzyloxy)-phenyl)-5-fluoro-5,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 118217219cis-Tert-butyl 4-(4-(benzyloxy)phenyl)-3-fluoropiperidine-1-carboxylateYield 77.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To 10% Pd/C (220 mg) under nitrogen was added a soln of tert-butyl 4-(4-(benzyloxy)-phenyl)-5-fluoro-5,6-dihydropyridine-1(2H)-carboxylate (1.35 g, 3.5 mmol) in ethyl acetate (20 mL). The mixture was stirred at rt under a hydrogen atmosphere at balloon pressure for 45 min. The Pd/C was removed by filtration, and the filtrate was concentrated. The residue was purified via silica gel chromatography (40 g of silica gel) eluting with a gradient of 0-100% ethyl acetate in hexanes to give the product cis-tert-butyl 4-(4-(benzyloxy)phenyl)-3-fluoropiperidine-1-carboxylate (1.05 g, 2.7 mmol, 77% yield). LC/MS (Conditions CZ-1) (M−t-butyl, AcCN+H)+=371.25. RT=1.504 min; 1H NMR (500 MHz, chloroform-d) δ 7.45 (d, J=7.6 Hz, 2H), 7.40 (t, J=7.5 Hz, 2H), 7.34 (t, J=7.0 Hz, 1H), 7.22 (d, J=8.4 Hz, 2H), 6.96 (ddd, J=8.9, 2.7, 2.0 Hz, 2H), 5.07 (s, 2H), 4.79-4.60 (m, 1H), 4.55-4.23 (m, 2H), 3.08-2.81 (m, 2H), 2.75 (ddd, J=36.0, 13.4, 3.1 Hz, 1H), 2.21 (qd, J=12.9, 4.3 Hz, 1H), 1.69 (d, J=11.7 Hz, 1H), 1.59 (s, 3H), 1.51 (s, 9H). The structure of this compound was verified by single-crystal X-ray analysis.

Workup

  1. customThe Pd/C was removed by filtration
  2. concentrationthe filtrate was concentrated
  3. customThe residue was purified via silica gel chromatography (40 g of silica gel)
  4. washeluting with a gradient of 0-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-b74b0e8bd9f64c98b1451a4d04fb6720
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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