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

HRID 2168920Notes

Reaction equation

HRID 2168920 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

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-carboxylateYield 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-79a72db3b2ae47c0b68e8861a712df11
Source dataset
uspto-grants-2015_06
Patent number
US09045436B2

Reaction notes

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