Methyl 1-(naphthalen-1-ylsulfonyl)piperidine-4-carboxylate → 1-(1-(Naphthalen-1-ylsulfonyl)piperidin-4-yl)cyclopropanol

HRID 2356214Notes

Reaction equation

HRID 2356214 reaction equation
[CH2:1]([Mg]Br)[CH3:2].[C:5]1([S:15]([N:18]2[CH2:23][CH2:22][CH:21]([C:24](OC)=[O:25])[CH2:20][CH2:19]2)(=[O:17])=[O:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7][CH:6]=1>O1CCCC1.CC(C)[O-].CC(C)[O-].CC(C)[O-].C[Ti+3]>[C:5]1([S:15]([N:18]2[CH2:19][CH2:20][CH:21]([C:24]3([OH:25])[CH2:2][CH2:1]3)[CH2:22][CH2:23]2)(=[O:16])=[O:17])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7][CH:6]=1

Participants

5

Reactant 2

HCID 11950392Methyl 1-(naphthalen-1-ylsulfonyl)piperidine-4-carboxylateHCID 178418443HCID 178418443, compound

Product 1

HCID 119503941-(1-(Naphthalen-1-ylsulfonyl)piperidin-4-yl)cyclopropanolYield 35.2%

Reagents, catalysts & solvents 2

HCID 178459133HCID 178459133, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Ethylmagnesium bromide (0.110 mL, 3.0 M in THF, 0.330 mmol) was added dropwise to a stirring solution of methyl 1-(naphthalen-1-ylsulfonyl)piperidine-4-carboxylate (0.100 g, 0.30 mmol) and methyltitanium triisopropoxide (0.300 mL, 1.0 M in THF, 0.300 mmol) in tetrahydrofuran (3 mL) at 0° C. The reaction mixture was allowed to warm to ambient temperature over 2 h then quenched with water (15 mL). The resulting flocculent solution was diluted with ethyl acetate (15 mL) and filtered through Celite. The filtrate was extracted with ethyl acetate (2×10 mL). The combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography on SiO2 eluted with hexanes/ethyl acetate (1:1) to yield 0.035 g (35%) of the title compound as a white foam. 1H NMR (400 MHz, Chloroform-d) δ, ppm: 0.36-0.41 (m, 2 H), 0.67-0.71 (m, 2H), 0.90-0.98 (m, 1 H), 1.72 (dd, J=13.89, 1.26 Hz, 2 H), 2.49 (td, J=12.51, 2.53 Hz, 2 H), 3.91-4.02 (m, 2 H), 7.54-7.60 (m, 3 H), 7.92 (d, J=8.34 Hz, 1 H), 8.06 (d, J=8.08 Hz, 1 H), 8.21 (d, J=7.33 Hz, 1 H), 8.76 (s, 1 H); ESI-MS: m/z 332.3 (M+H)+.

Workup

  1. customthen quenched with water (15 mL)
  2. additionThe resulting flocculent solution was diluted with ethyl acetate (15 mL)
  3. filtrationfiltered through Celite
  4. extractionThe filtrate was extracted with ethyl acetate (2×10 mL)
  5. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography on SiO2
  8. washeluted with hexanes/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-255f06bbf0e749c5bb7ad73addb877d5
Source dataset
uspto-grants-2010_07
Patent number
US07759339B2

Reaction notes

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