benzyl 4-((1R,2S)-2-(2-(4-(1H-tetrazol-1-yl)phenoxy)ethyl)cyclopropyl)piperidine-1-carboxylate → 4-((1R,2S)-2-(2-(4-(1H-tetrazol-1-yl)phenoxy)ethyl)cyclopropyl)piperidine

HRID 1850733Notes

Reaction equation

HRID 1850733 reaction equation
[N:1]1([C:6]2[CH:33]=[CH:32][C:9]([O:10][CH2:11][CH2:12][C@@H:13]3[CH2:15][C@@H:14]3[CH:16]3[CH2:21][CH2:20][N:19](C(OCC4C=CC=CC=4)=O)[CH2:18][CH2:17]3)=[CH:8][CH:7]=2)[CH:5]=[N:4][N:3]=[N:2]1>[Pd].C(O)C>[N:1]1([C:6]2[CH:7]=[CH:8][C:9]([O:10][CH2:11][CH2:12][C@@H:13]3[CH2:15][C@@H:14]3[CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[CH:32][CH:33]=2)[CH:5]=[N:4][N:3]=[N:2]1

Participants

4

Reactant 1

HCID 86711179benzyl 4-((1R,2S)-2-(2-(4-(1H-tetrazol-1-yl)phenoxy)ethyl)cyclopropyl)piperidine-1-carboxylate2×

Product 1

HCID 867111854-((1R,2S)-2-(2-(4-(1H-tetrazol-1-yl)phenoxy)ethyl)cyclopropyl)piperidine

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

Benzyl 4-((1R,2S)-2-(2-(4-(1H-tetrazol-1-yl)phenoxy)ethyl)cyclopropyl)piperidine-1-carboxylate (Intermediate 13; 2.90 g, 6.49 mmol) and palladium on activated carbon (10%, wet, 600 mg) in ethanol (50 mL) were stirred under an atmosphere of hydrogen (1 atm) at RT for 2 h. The mixture was filtered (glass wool filter paper, Whatman 1821 110), and washed with ethanol. The filtrate was concentrated to dryness under reduced pressure. The residue was purified by silica gel chromatography (120 g RediSep, eluted with a gradient of dichloromethane/CMA, 9:1, 500 mL; 4:1, 1 L; 7:3, 3 L provide the title compound as an off-white solid. 1H NMR (300 MHz, CDCl3) δ 8.90 (s, 1H), 7.59 (d, J=9.0 Hz, 2H), 7.07 (d, J=9.0 Hz, 2H), 4.12 (t, J=6.7 Hz, 2H), 3.17-3.00 (m, 2H), 2.65-2.45 (m, 2H), 2.25-2.05 (m, 1H), 1.90-1.70 (m, 3H), 1.63-1.47 (m, 1H), 1.43-1.23 (m, 2H), 1.02-0.84 (m, 2H), 0.74-0.57 (m, 2H), −0.12 (q, J=4.3 Hz, 1H). MS (Multimode) m/z 314 [M+H]+.

Workup

  1. filtrationThe mixture was filtered
  2. filtration(glass wool filter paper, Whatman 1821 110)
  3. washwashed with ethanol
  4. concentrationThe filtrate was concentrated to dryness under reduced pressure
  5. customThe residue was purified by silica gel chromatography (120 g RediSep
  6. washeluted with a gradient of dichloromethane/CMA, 9:1, 500 mL

Sources & evidence

ORD record
ord-4547ad99d37942f8aa619e2b56083964
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

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