Triphenylphosphine → 1,1-Dimethylethyl 4-({[4'-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinecarboxylate

HRID 423454

Reaction equation

HRID 423454 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[C:18]([N:25]1[CH2:30][CH2:29][CH:28]([CH2:31]O)[CH2:27][CH2:26]1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1.CCOC(C)=O>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:31][CH:28]3[CH2:29][CH2:30][N:25]([C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:26][CH2:27]3)=[CH:13][CH:12]=2)=[CH:9][CH:10]=1)(=[O:3])=[O:4]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylateHCID 149826764'-(Methylsulfonyl)-[1,1'-biphenyl]-4-ol

Product 1

HCID 591777911,1-Dimethylethyl 4-({[4'-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinecarboxylateYield 74.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4′-(methylsulfonyl)-4-biphenylol (0.15 g, 0.60 mmol), N-Boc-4-piperidinemethanol (0.14 g, 0.60 mmol) and Ph3P (0.16 g, 0.66 mmol) in THF (4 mL) was cooled to −20° C. Diisopropyl azodicarboxylate (0.13 g, 94%, 0.60 mmol) in THF (1 mL) was added dropwise. The reaction mixture was kept between −20° C. and 0° C. for 3 h, then allowed to warm up to ambient temperature, and stirred at ambient temperature overnight. The mixture was diluted with EtOAc, washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a yellow oil. The crude product was purified by chromatography on a silica gel column eluted with 40% EtOAc/hexane to give 0.20 g (74%) of the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ 7.97 (d, 2H, J=7.6 Hz), 7.83 (d, 2H, J=7.3 Hz), 7.64 (d, 2H, J=7.6 Hz), 7.03 (d, 2H, J=7.8 Hz), 4.15-4.05 (m, 2H), 3.90 (d, 2H, J=6.4 Hz), 3.13 (s, 3H), 2.90-2.70 (bs, 2H), 2.10-1.95 (m, 1H), 1.90-1.80 (m, 2H), 1.46 (s, 9H), 1.35-1.20 (m, 2H); LRMS (ESI), m/z 446 (M+H).

Workup

  1. washwashed with saturated aqueous NaHCO3 and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated
  5. customto give the crude product as a yellow oil
  6. customThe crude product was purified by chromatography on a silica gel column
  7. washeluted with 40% EtOAc/hexane

Sources & evidence

ORD record
ord-5eeb2d2fda774b72852deff78effaa6a
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Linked notes

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