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Ethanol → tert-Butyl (3R,5S)-3-(hydroxymethyl)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl)(2-methylpropyl)amino]piperidine-1-carboxylate

HRID 1259930
Notes
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Reaction equation

HRID 1259930 reaction equation
[BH4-].[Na+].C(O)C.[Cl-].[Ca+2].[Cl-].[CH3:9][O:10][CH2:11][CH2:12][CH2:13][CH2:14][N:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N:17]=[C:16]1[C:24]([N:26]([CH2:44][CH:45]([CH3:47])[CH3:46])[C@@H:27]1[CH2:32][N:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:30][C@H:29]([C:40](OC)=[O:41])[CH2:28]1)=[O:25]>C1COCC1.O.C(OCC)(=O)C>[OH:41][CH2:40][C@@H:29]1[CH2:28][C@H:27]([N:26]([C:24]([C:16]2[N:15]([CH2:14][CH2:13][CH2:12][CH2:11][O:10][CH3:9])[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[N:17]=2)=[O:25])[CH2:44][CH:45]([CH3:47])[CH3:46])[CH2:32][N:31]([C:33]([O:35][C:36]([CH3:38])([CH3:37])[CH3:39])=[O:34])[CH2:30]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 702EthanolHCID 4311764Sodium borohydrideHCID 5284359Calcium ChlorideHCID 583555501-tert-Butyl 3-methyl(3R,5S)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-1,3-dicarboxylate

Product 1

HCID 58355672tert-Butyl (3R,5S)-3-(hydroxymethyl)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl)(2-methylpropyl)amino]piperidine-1-carboxylate
Yield 47.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Sodium borohydride (4.45 g) was suspended in THF (25 ml)-ethanol (75 ml), and calcium chloride (6.5 g) was added. After stirring at 0° C. for 1 hr, a solution of 1-tert-butyl 3-methyl (3R,5S)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-1,3-dicarboxylate (4.0 g) in THF (50 ml) was added. After stirring at room temperature for 12 hr, ethyl acetate (150 ml) and water (50 ml) were slowly added in this order, and the mixture was filtered. The organic layer of the filtrate was partitioned, washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was dried under reduced pressure to give the object product (1.8 g).

Workup

  1. additionwas added
  2. stirringAfter stirring at room temperature for 12 hr
  3. filtrationthe mixture was filtered
  4. customThe organic layer of the filtrate was partitioned
  5. washwashed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customThe residue was dried under reduced pressure

Sources & evidence

ORD record
ord-01bf91ab3910473e86b4e00a0edade99
Source dataset
uspto-grants-2013_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08466282B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes