Dichloromethane → HCID 68817252, compound

HRID 736796Notes

Reaction equation

HRID 736796 reaction equation
C([N:8]([C@@H](C1C=CC=CC=1)C)[C@@H:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][C@:10]1([CH3:26])[C:22]([O:24][CH3:25])=[O:23])C1C=CC=CC=1.[CH2:35]([O:42][C:43]1[CH:48]=[CH:47][C:46]([S:49](Cl)(=[O:51])=[O:50])=[CH:45][CH:44]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C(Cl)Cl.C(=O)(O)[O-].[Na+]>C(O)=O.CO.[Pd]>[CH2:35]([O:42][C:43]1[CH:48]=[CH:47][C:46]([S:49]([NH:8][C@@H:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:11][C@:10]2([CH3:26])[C:22]([O:24][CH3:25])=[O:23])(=[O:51])=[O:50])=[CH:45][CH:44]=1)[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 47383854-(Benzyloxy)benzene-1-sulfonyl chlorideHCID 68817302HCID 68817302, compound

Product 1

HCID 68817252HCID 68817252, compoundYield 85.2%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 284Formic AcidSolventHCID 887MethanolSolvent

Procedure

(3S,4R)-1-tert-Butyl 3-methyl 4-(benzyl((R)-1-phenylethyl)amino)-3-methylpiperidine-1,3-dicarboxylate (4.777 g, 10.24 mmol) was taken up in 100 mL of 4.4% formic acid in methanol. Palladium on Carbon (10%, 1.059 g) was added and the reaction mixture was stirred under a nitrogen atmosphere for 2 h at room temperature. Filtration through celite gave a colorless solution that was concentrated to give a colorless oil. The oil was combined with 4-(benzyloxy)benzene-1-sulfonyl chloride (4.377 g, 15.48 mmol) and equivalent volumes of CH2Cl2 and saturated sodium bicarbonate, and the resultant biphasic mixture was stirred vigorously overnight. The organic layer was separated and the remaining aqueous phase was washed with CH2Cl2 (3×). the organic extracts were combined, dried over Na2SO4 and concentrated to give a beige solid that was purified by chromatography on silica gel eluting with 30% ethyl acetate/hexanes to give (3S,4R)-1-tert-butyl 3-methyl 4-(4-(benzyloxy)phenylsulfonamido)-3-methylpiperidine-1,3-dicarboxylate as a white solid (4.523 g, 8.72 mmol, 85%). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1.14 (s, 3 H) 1.37-1.48 (m, 11H) 1.78 (s, 1H) 2.02-2.05 (m, 3H) 2.51 (s, 1H) 3.08-3.16 (m, 1H) 3.65 (s, 3H) 4.48 (s, 1H) 5.11 (s, 2H) 5.65 (d, J=9.60 Hz, 1H) 7.01-7.06 (m, 2H) 7.31-7.43 (m, 6H) 7.78-7.82 (m, 2H).

Workup

  1. filtrationFiltration through celite
  2. customgave a colorless solution that
  3. concentrationwas concentrated
  4. customto give a colorless oil
  5. stirringthe resultant biphasic mixture was stirred vigorously overnight
  6. customThe organic layer was separated
  7. washthe remaining aqueous phase was washed with CH2Cl2 (3×)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customto give a beige solid
  11. customthat was purified by chromatography on silica gel eluting with 30% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-feed51d39d864bb0900b3fa3266cbd35
Source dataset
uspto-grants-2009_09
Patent number
US07595327B2

Reaction notes

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