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Formaldehyde → tert-Butyl 3-[{6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}(methyl)amino]benzoate

HRID 446541
Notes
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Reaction equation

HRID 446541 reaction equation
[C:1]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]([O:10][CH:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][N:19]([CH3:41])[C:20](=[O:40])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:26][C:27]2[CH:28]=[C:29]([CH:37]=[CH:38][CH:39]=2)[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:13][CH2:12]1)=[O:9].C=O.[C:50](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(O)C.C(OCC)(=O)C.C1(C)C=CC=CC=1>[C:1]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]([O:10][CH:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][N:19]([CH3:41])[C:20](=[O:40])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][N:26]([CH3:50])[C:27]2[CH:28]=[C:29]([CH:37]=[CH:38][CH:39]=2)[C:30]([O:32][C:33]([CH3:34])([CH3:35])[CH3:36])=[O:31])[CH2:13][CH2:12]1)=[O:9]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 86663445tert-Butyl 3-({6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}amino)benzoate

Product 1

HCID 86663446tert-Butyl 3-[{6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}(methyl)amino]benzoate
Yield 96%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Moisture was removed from a mixture of the compound (120 mg, 0.205 mmol) obtained in Example 43a and a 35% aqueous formaldehyde solution (85 μL, 1.02 mmol) azeotropically with toluene 3 times. The resulting mixture was dissolved in ethanol (6 mL), sodium triacetoxyborohydride (65 mg, 0.307 mmol) was added under ice cooling, and the mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours. After the reaction was completed, a saturated aqueous sodium hydrogencarbonate solution was added, and ethyl acetate was further added to separate the layers. The resulting organic layer was separated, washed with saturated sodium chloride solution, and then dried with anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:methanol, 10:1, v/v) to give the title compound (118 mg; yield, 96%) as a colorless oily substance.

Workup

  1. customto separate the layers
  2. customThe resulting organic layer was separated
  3. washwashed with saturated sodium chloride solution
  4. dry with materialdried with anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by NH silica gel column chromatography (ethyl acetate:methanol, 10:1, v/v)

Sources & evidence

ORD record
ord-13f3afebe1974a39b7c3c1e5d264bfdf
Source dataset
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08476253B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes