Water → tert-Butyl 3-(morpholine-4-sulfonyl)[1,4'-bipiperidine]-1'-carboxylate

HRID 489903Notes

Reaction equation

HRID 489903 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([S:7]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)(=[O:9])=[O:8])[CH2:2]1.O=[C:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1.C([BH3-])#N.[Na+].O>C(O)C.CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C>[C:26]([O:25][C:23]([N:20]1[CH2:21][CH2:22][CH:17]([N:1]2[CH2:6][CH2:5][CH2:4][CH:3]([S:7]([N:10]3[CH2:11][CH2:12][O:13][CH2:14][CH2:15]3)(=[O:8])=[O:9])[CH2:2]2)[CH2:18][CH2:19]1)=[O:24])([CH3:29])([CH3:27])[CH3:28]

Participants

7

Reactant 4

HCID 962WaterHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5003444Sodium cyanoborohydrideHCID 222631374-(Piperidine-3-sulfonyl)morpholine

Product 1

HCID 69695450tert-Butyl 3-(morpholine-4-sulfonyl)[1,4'-bipiperidine]-1'-carboxylateYield 41.1%

Reagents, catalysts & solvents 2

HCID 178460666HCID 178460666, compoundCatalystHCID 702EthanolSolvent2×

Procedure

A mixture of the 4-(piperidine-3-sulfonyl)-morpholine (710 mg, 3.03 mmol), tert-butyl 4-oxo-1-piperidinecarboxylate (1 eq, 605 mg) and Ti(OiPr)4 (1.25 eq, 1.12 mL) was stirred under nitrogen at ambient temperature for 1 hr. A solution of sodium cyanoborohydride (0.7 eq, 133 mg) in anhydrous ethanol (3 mL) was added and the clear solution was stirred overnight. Water (0.6 mL) was added followed by sufficient ethanol to permit stirring. The thick suspension was filtered through Celite® rising through with ethanol and the filtrate was evaporated to a cloudy oil which was redissolved in dichloromethane/ethanol, a few drops of water added and the mixture was filtered through Celite®. The filtrate was diluted with toluene, evaporated under vacuum and the residue purified by chromatography on silica gel eluting with 2.5% methanol-dichloromethane. The desired fractions were combined, evaporated under vacuum and the residue chromatographed on silica gel eluting with 2.5% methanol-dichloromethane to give 3-(morpholine-4-sulfonyl)-[1,4′]bipiperidinyl-1′-carboxylic acid tert-butyl ester (520 mg, 41%).

Workup

  1. stirringthe clear solution was stirred overnight
  2. stirringto permit stirring
  3. filtrationThe thick suspension was filtered through Celite®
  4. customthe filtrate was evaporated to a cloudy oil which
  5. dissolutionwas redissolved in dichloromethane/ethanol
  6. additiona few drops of water added
  7. filtrationthe mixture was filtered through Celite®
  8. additionThe filtrate was diluted with toluene
  9. customevaporated under vacuum
  10. customthe residue purified by chromatography on silica gel eluting with 2.5% methanol-dichloromethane
  11. customevaporated under vacuum
  12. customthe residue chromatographed on silica gel eluting with 2.5% methanol-dichloromethane

Sources & evidence

ORD record
ord-303d45bdeeda4c98ac9c67313322cdfe
Source dataset
uspto-grants-2005_12
Patent number
US06979741B2

Reaction notes

Loading…