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

HRID 1467216Notes

Reaction equation

HRID 1467216 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 183d) (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-a37de6173af94a1186bd8396b4357623
Source dataset
uspto-grants-2015_04
Patent number
US09000054B2

Reaction notes

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