9-Fluorenylmethyl chloroformate → HCID 21363631, compound

HRID 987097Notes

Reaction equation

HRID 987097 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH:16]([C:17](=[O:29])[NH:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:15][CH2:14][CH2:13][CH:12]1[CH2:30][CH:31]([O:34][CH3:35])[O:32][CH3:33])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H][H].ClC(OC[CH:43]1[C:55]2C=CC=C[C:50]=2C2[C:44]1=[CH:45][CH:46]=[CH:47]C=2)=O.C([O-])(O)=O.[Na+].OS([O-])(=O)=O.[K+]>CO.O.[Pd]>[CH:4]1[C:3]2[CH:2]([CH2:1][O:8][C:9]([N:11]3[CH:16]([C:17](=[O:29])[NH:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH2:15][CH2:14][CH2:13][CH:12]3[CH2:30][CH:31]([O:34][CH3:35])[O:32][CH3:33])=[O:10])[C:7]3[C:45](=[CH:44][CH:43]=[CH:55][CH:50]=3)[C:46]=2[CH:47]=[CH:6][CH:5]=1

Participants

9

Reactant 5

HCID 343679-Fluorenylmethyl chloroformateHCID 516892Sodium BicarbonateHCID 516920Potassium bisulfateHCID 543007762-(2,2-Dimethoxy-ethyl)-6-(4-phenyl-butylcarbamoyl)-piperidine-1-carboxylic Acid Benzyl Ester2×HCID 178418361HCID 178418361, compound

Product 1

HCID 21363631HCID 21363631, compoundYield 100.5%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

2-(2,2-Dimethoxy-ethyl)-6-(4-phenyl-butylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester (Compound 242, 0.887 g, 1.83 mmol) was dissolved in methanol (50 mL). Palladium (10%) on activated carbon (0.09 g) was added. Hydrogen was applied via Parr apparatus, and the reaction was shaken at 50 psi for 15 hours. The black suspension was then filtered through compacted Celite, and methanol was removed. The residue was dissolved in dioxane (25 mL). 9-Fluorenylmethyl chloroformate (0.473 g, 1.83 mmol) was added, followed by NaHCO3 (0.307 g, 3.66 mmol) dissolved in water (7 mL). The reaction was stirred at room temperature for 10 hours, poured into ice and 5% KHSO4 solution, and then extracted with CHCl3 (2×100 mL). Flash chromatographic purification of the residue (1:2 EtOAc/hexanes) gave Compound 243 (1.050 g, 100%). Rf=0.59 (1:1 EtOAc/hexanes).

Workup

  1. filtrationThe black suspension was then filtered
  2. customwas removed
  3. dissolutionThe residue was dissolved in dioxane (25 mL)
  4. stirringThe reaction was stirred at room temperature for 10 hours
  5. extractionextracted with CHCl3 (2×100 mL)
  6. customFlash chromatographic purification of the residue (1:2 EtOAc/hexanes)

Sources & evidence

ORD record
ord-9fe26659f65340d8a2752a82b433d8cd
Source dataset
uspto-grants-2003_10
Patent number
US06630472B1

Reaction notes

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