Tetrahydrofuran → tert-butyl N-(1-(hydroxymethyl)cyclopropyl)carbamate

HRID 2204994Notes

Reaction equation

HRID 2204994 reaction equation
Cl.[NH2:2][C:3]1([C:6]([O:8]CC)=O)[CH2:5][CH2:4]1.[C:11](=O)([O:17]C(C)(C)C)[O:12][C:13]([CH3:16])([CH3:15])[CH3:14].C(N(CC)CC)C.[Li+].[BH4-].C1COCC1>CCO.CN(C1C=CN=CC=1)C>[OH:8][CH2:6][C:3]1([NH:2][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:4][CH2:5]1

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 386203Ethyl 1-aminocyclopropane-1-carboxylate hydrochlorideHCID 4148881Lithium borohydride2×HCID 10219638Carbonic acid, bis(1,1-dimethylethyl) ester

Product 1

HCID 11286907tert-butyl N-(1-(hydroxymethyl)cyclopropyl)carbamate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 702EthanolSolvent

Procedure

To a solution of ethyl 1-aminocyclopropanecarboxylate hydrochloride (1 eq) in EtOH (0.3 M) at room temperature was added di-tert-butyl carbonate (1.5 eq), triethylamine (2 eq), and DMAP (0.05 eq). The reaction was stirred at room temperature overnight. The reaction mixture was concentrated en vaccuo; and the residue was diluted in ethyl acetate. The organic solution was washed 1:1 saturated aqueous NH4Cl/water, brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The material was taken up in THF (0.3 M) and cooled to 0° C. To this solution was added 2 M LiBH4 in THF (4 eq). The reaction was warmed to room temperature and stirred for 4 hours, at which time more 2 M LiBH4 (1.3 eq) was added, and stirred overnight. The reaction mixture was cooled to 0° C. and slowly quenched with MeOH over 10 minutes and then water. The solution was stirred for 10 minutes; and precipitates appeared. The precipitates were filtered and rinsed with ethyl acetate. The filtrate was washed with water, brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using a gradient of 0-75% ethyl acetate in hexanes to give the product.

Workup

  1. concentrationThe reaction mixture was concentrated en vaccuo
  2. additionand the residue was diluted in ethyl acetate
  3. washThe organic solution was washed 1:1 saturated aqueous NH4Cl/water, brine
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationconcentrated en vaccuo
  6. temperaturecooled to 0° C
  7. temperatureThe reaction was warmed to room temperature
  8. additionwas added
  9. stirringstirred overnight
  10. temperatureThe reaction mixture was cooled to 0° C.
  11. customslowly quenched with MeOH over 10 minutes
  12. stirringThe solution was stirred for 10 minutes
  13. customand precipitates
  14. filtrationThe precipitates were filtered
  15. washrinsed with ethyl acetate
  16. washThe filtrate was washed with water, brine
  17. dry with materialdried over anhydrous MgSO4
  18. concentrationconcentrated en vaccuo
  19. customThe crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)
  20. customto give the product

Sources & evidence

ORD record
ord-4bd8f2676bbd4f0ca4577900b95e1917
Source dataset
uspto-grants-2016_06
Patent number
US09365506B2

Reaction notes

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