Trichloroisocyanuric Acid → (R)-tert-butyl 3-((S)-2-(3-chlorophenyl)-6-oxotetrahydro-2H-pyran-2-yl)piperidine-1-carboxylate

HRID 451670Notes

Reaction equation

HRID 451670 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@:8]([C@@H:15]2[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16]2)([OH:14])[CH2:9][CH2:10][CH2:11][CH2:12][OH:13])[CH:5]=[CH:6][CH:7]=1.C([O-])(O)=O.[Na+].[Na+].[Br-].ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O>CC(C)=O.CC1(C)N([O])C(C)(C)CCC1.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@@:8]2([C@@H:15]3[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16]3)[CH2:9][CH2:10][CH2:11][C:12](=[O:13])[O:14]2)[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 6909Trichloroisocyanuric AcidHCID 253881Sodium BromideHCID 516892Sodium BicarbonateHCID 59201684(R)-tert-butyl 3-((S)-1-(3-chlorophenyl)-1,5-dihydroxypentyl)piperidine-1-carboxylate

Product 1

HCID 59201295(R)-tert-butyl 3-((S)-2-(3-chlorophenyl)-6-oxotetrahydro-2H-pyran-2-yl)piperidine-1-carboxylateYield 81.2%

Reagents, catalysts & solvents 3

HCID 2724126TempoCatalystHCID 180AcetoneSolventHCID 3776IsopropanolSolvent

Procedure

To a stirred solution of (R)-tert-butyl 3-((S)-1-(3-chlorophenyl)-1,5-dihydroxypentyl)piperidine-1-carboxylate (200 mg, 0.5 mmol) in acetone (3 mL) maintained at 0° C. was added an 15% aq NaHCO3 (2 mL), followed by solid NaBr (10.3 mg, 0.1 mmol) and TEMPO (1.56 mg, 0.01 mmol). Trichloroisocyanuric acid (231 mg, 1 mmol) was then slowly added at 0° C. The mixture was warmed to rt, stirred for 3 h and treated with 2-propanol (0.5 mL). The mixture was filtered through celite and the filtrate was concentrated in vacuo. The residue was partitioned between water and EtOAc and the aqueous phase was extracted with EtOAc (3×20 mL). The organic layers were combined, washed with brine, dried over Na2SO4 and concentrated under reduced pressure to provide (R)-tert-butyl 3-((S)-2-(3-chlorophenyl)-6-oxotetrahydro-2H-pyran-2-yl)piperidine-1-carboxylate (160 mg, 81%). 1H NMR (400 MHz, CDCl3): 1.12-1.45 (m, 3H), 1.46 (s, 9H), 1.58-1.81 (m, 6H), 2.22 (m, 2H), 2.42 (m, 2H), 2.56 (m, 2H), 4.05 (m, 1H), 4.36 (m, 1H), 7.16 (m, 1H), 7.27-7.32 (s, 1H). MS (E/Z): 394 (M+H+).

Workup

  1. filtrationThe mixture was filtered through celite
  2. concentrationthe filtrate was concentrated in vacuo
  3. customThe residue was partitioned between water and EtOAc
  4. extractionthe aqueous phase was extracted with EtOAc (3×20 mL)
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-06550951fec441f6bdc52d72fb380b01
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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