Hexamethylphosphoramide → 1-(Tert-butoxycarbonyl)-4-(4-phenylbutylidene)piperidine

HRID 2095422Notes

Reaction equation

HRID 2095422 reaction equation
[I-].C1([P+](C2C=CC=CC=2)(C2C=CC=CC=2)[CH2:9][CH2:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)C=CC=CC=1.CN(P(N(C)C)(N(C)C)=O)C.[Li]CCCC.O=[C:48]1[CH2:53][CH2:52][N:51]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:50][CH2:49]1>C1COCC1>[C:57]([O:56][C:54]([N:51]1[CH2:52][CH2:53][C:48](=[CH:9][CH2:10][CH2:11][CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:49][CH2:50]1)=[O:55])([CH3:60])([CH3:58])[CH3:59]

Participants

6

Reactant 4

HCID 12679HexamethylphosphoramideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 86642679Triphenyl(4-phenylbutyl)phosphonium iodideHCID 178418339Butyllithium

Product 1

HCID 593714671-(Tert-butoxycarbonyl)-4-(4-phenylbutylidene)piperidineYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of triphenyl(4-phenylbutyl)phosphonium iodide (975 mg, 1.87 mmol) in THF (8 mL) under Ar at −78° C. was added HMPA (1 mL) followed by n-BuLi (1.6 M in hexane; 1.28 mL, 2.05 mmol, 1.1 equiv.). After stirring at room temperature for 2 h, the mixture was cooled to −78° C. again, and tert-butyl 4-oxopiperidine-1-carboxylate (409 mg, 2.05 mmol, 1.1 equiv.) in THF (2 mL) was added. The mixture was allowed to warm to room temperature and to stand for 2 days. The reaction was quenched with H2O, and the mixture was extracted three times with EtOAc. The combined organic layers were washed with brine and dried over Na2SO4. After concentration, the residue was purified by CC (SiO2, hexane/EtOAc 10:1) to obtain 1-(tert-butoxycarbonyl)-4-(4-phenylbutylidene)piperidine (216 mg, 37%) as a pale yellow oil. 1H NMR (CDCl3, 400 MHz) δ 7.25 (m, 2H), 7.15 (m, 3H), 5.22 (t, 1H, J=7.2 Hz), 3.55 (m, 4H), 2.60 (t, 2H, J=8.0 Hz), 2.15 (m, 4H), 2.03 (m, 2H), 1.66 (m, 2H), 1.46 (s, 9H).

Workup

  1. temperaturethe mixture was cooled to −78° C. again
  2. temperatureto warm to room temperature
  3. waitto stand for 2 days
  4. customThe reaction was quenched with H2O
  5. extractionthe mixture was extracted three times with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationAfter concentration
  9. customthe residue was purified by CC (SiO2, hexane/EtOAc 10:1)

Sources & evidence

ORD record
ord-dd8dc7d90cdb47a69ede6dc73cd54966
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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