Sodium borohydride → 1-(hydroxymethyl)-N-propylcyclopropanecarboxamide

HRID 711800Notes

Reaction equation

HRID 711800 reaction equation
[CH2:1]([NH:4][C:5]([C:7]1([C:10](OCC)=[O:11])[CH2:9][CH2:8]1)=[O:6])[CH2:2][CH3:3].[BH4-].[Na+]>CCO>[OH:11][CH2:10][C:7]1([C:5]([NH:4][CH2:1][CH2:2][CH3:3])=[O:6])[CH2:8][CH2:9]1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 66746001Ethyl 1-(propylcarbamoyl)cyclopropanecarboxylate

Product 1

HCID 667460451-(hydroxymethyl)-N-propylcyclopropanecarboxamideYield 88%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of ethyl 1-(propylcarbamoyl)cyclopropanecarboxylate (Example 198d) (1.65 g, 8.27 mmol) in EtOH (70 mL) was added NaBH4 (0.97 g, 25.64 mmol) at rt. The obtained mixture was stirred at rt over 2 days, quenched with 1.5M HCl and concentrated under reduced pressure. The concentrated mixture was extracted with EtOAc (4×70 mL), the combined extract was washed with saturated NaHCO3 and brine, and was dried over MgSO4. The filtrate was evaporated and the residue was purified by chromatography on silica gel using the solvent gradient hexanes→hexanes/EtOAc (1:9), to furnish 1.14 g (88%) of the product as a white solid. 1H-NMR (400 MHz, DMSO-d6) δ 7.49 (broad s, 1H), 5.09 (broad s, 1H), 3.49 (s, 2H), 3.05 (q, J=6.4 Hz, 2H), 1.41 (hex, J=7.6 Hz, 2H), 0.86-0.91 (m, 2H), 0.83 (t, J=7.2 Hz, 3H), 0.55-0.60 (m, 2H).

Workup

  1. customquenched with 1.5M HCl
  2. concentrationconcentrated under reduced pressure
  3. extractionThe concentrated mixture was extracted with EtOAc (4×70 mL)
  4. extractionthe combined extract
  5. washwas washed with saturated NaHCO3 and brine
  6. dry with materialwas dried over MgSO4
  7. customThe filtrate was evaporated
  8. customthe residue was purified by chromatography on silica gel using the solvent gradient hexanes→hexanes/EtOAc (1:9)

Sources & evidence

ORD record
ord-7f311d21c7c44756ac1daf0b3082ccd5
Source dataset
uspto-grants-2015_11
Patent number
US09181276B2

Reaction notes

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