Acetic Acid → HCID 66747178, compound

HRID 1019872Notes

Reaction equation

HRID 1019872 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([CH:11]=O)=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([NH:26][CH3:27])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C(O)(=O)C.C([BH3-])#N.[Na+]>ClCCCl.CO.C(OCC)(=O)C.C1CCCCC1>[C:13]([O:17][C:18]([N:20]1[CH2:21][CH2:22][CH:23]([N:26]([CH2:11][C:9]2[CH:8]=[CH:7][C:6]3[O:1][CH2:2][CH2:3][O:4][C:5]=3[CH:10]=2)[CH3:27])[CH2:24][CH2:25]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 2481272,3-Dihydro-1,4-benzodioxin-6-carbaldehydeHCID 5003444Sodium cyanoborohydrideHCID 15380702tert-Butyl 4-(methylamino)piperidine-1-carboxylate

Product 1

HCID 66747178HCID 66747178, compoundYield 57.8%

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolventHCID 8078CyclohexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2,3-dihydro-benzo[1,4]dioxine-6-carbaldehyde (153 mg, 0.93 mmol, 1.0 eq) is added at room temperature to a stirred solution of 4-methylamino-piperidine-1-carboxylic acid tert-butyl ester (200 mg, 0.93 mmol, 1.0 eq) in 1,2-dichloroethane (8 mL) and methanol (2 mL), followed by acetic acid (61 μL, 1.07 mmol, 1.15 eq) and sodium cyanoborohydride (76 mg, 1.21 mmol, 1.3 eq). After 15 hours stirring at room temperature, the reaction mixture is extracted with dichloromethane (3×20 mL) and a saturated sodium hydrogen carbonate aqueous solution (20 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel, eluent: cyclohexane:ethyl acetate, 3:1 to 1:3, v/v) to afford 4-[(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-methyl-amino]-piperidine-1-carboxylic acid tert-butyl ester as an off-white oil (195 mg, 55% yield).

Workup

  1. extractionthe reaction mixture is extracted with dichloromethane (3×20 mL)
  2. dry with materialThe combined organic layers are dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a residue that
  6. customis purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-e1c7f154d66240e5b1f71689db1a8505
Source dataset
uspto-grants-2014_05
Patent number
US08716280B2

Reaction notes

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