Sodium borohydride → tert-butyl (3S,5R)-3-[[[1-(2-hydroxyethyl)-1H-benzimidazol-2-yl]carbonyl](2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

HRID 2168979Notes

Reaction equation

HRID 2168979 reaction equation
[Cl-].[Ca+2].[Cl-].[BH4-].[Na+].C[O:7][C:8](=O)[CH2:9][N:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]=[C:11]1[C:19]([N:21]([CH2:43][CH:44]([CH3:46])[CH3:45])[C@H:22]1[CH2:27][C@@H:26]([C:28]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)=[O:29])[CH2:25][N:24]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:23]1)=[O:20]>C(O)C.C1COCC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[OH:7][CH2:8][CH2:9][N:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]=[C:11]1[C:19]([N:21]([CH2:43][CH:44]([CH3:46])[CH3:45])[C@H:22]1[CH2:27][C@@H:26]([C:28]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)=[O:29])[CH2:25][N:24]([C:36]([O:38][C:39]([CH3:40])([CH3:41])[CH3:42])=[O:37])[CH2:23]1)=[O:20]

Participants

7

Reactant 3

HCID 4311764Sodium borohydrideHCID 5284359Calcium ChlorideHCID 58355362tert-butyl (3S,5R)-3-[[[1-(2-methoxy-2-oxoethyl)-1H-benzimidazol-2-yl]carbonyl](2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

Product 1

HCID 58355342tert-butyl (3S,5R)-3-[[[1-(2-hydroxyethyl)-1H-benzimidazol-2-yl]carbonyl](2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylateYield 77.5%

Reagents, catalysts & solvents 3

HCID 311Citric AcidSolventHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Calcium chloride (650 mg) was suspended in ethanol (80 ml) and sodium borohydride (740 mg) was added at 0° C. After stirring at 0° C. for 15 min, a solution of tert-butyl (3S,5R)-3-[[[1-(2-methoxy-2-oxoethyl)-1H-benzimidazol-2-yl]carbonyl](2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (1.15 g) in THF (80 ml) was added dropwise. After stirring at room temperature for 2 hr, the reaction mixture was diluted with 10% aqueous citric acid solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel chromatography, and a fraction eluted with ethyl acetate-hexane (1:9-1:0)-ethyl acetate-methanol (85:15) was concentrated under reduced pressure to give the object product (849 mg).

Workup

  1. stirringAfter stirring at room temperature for 2 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated aqueous sodium hydrogen carbonate
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. washa fraction eluted with ethyl acetate-hexane (1:9-1:0)-ethyl acetate-methanol (85:15)
  7. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-2c1f9e3f918e4f3b9bf5fcadb7247204
Source dataset
uspto-grants-2015_06
Patent number
US09045436B2

Reaction notes

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