Sodium borohydride → (S)-(-)-2-(Boc-amino)-1,4-butanediol

HRID 993477Notes

Reaction equation

HRID 993477 reaction equation
C([O:3][C:4](=O)[C@H:5]([CH2:14][C:15](OCC)=[O:16])[NH:6][C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])C.[BH4-].[Na+]>C(O)C.[Cl-].[Na+].O>[C:10]([O:9][C:7]([NH:6][C@@H:5]([CH2:14][CH2:15][OH:16])[CH2:4][OH:3])=[O:8])([CH3:13])([CH3:12])[CH3:11]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 10957183Diethyl (tert-butoxycarbonyl)-L-aspartate

Product 1

HCID 2734850(S)-(-)-2-(Boc-amino)-1,4-butanediolYield 73.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
25 °C

Procedure

A stirred solution of (S)-N-BOC diethyl Laspartate 3 (47.41 g, 0.16 mol) in absolute ethanol (770 ml) was cooled in ice, then sodium borohydride (60.8 g, 1.6 mol) was added in 10 g portions. The cooling bath was removed when the reaction subsided, and the reaction mixture was heated slowly to reflux for 1 h; after this time TLC (EtOAc-EtOH 3:1) analysis indicated complete consumption of the starting material. The reaction mixture was cooled to 25° C., and the lumps formed were broken-up to give a slurry that was poured into brine (450 ml). The mixture was filtered, the filtrate concentrated in vacuum to ca. 100 ml, and was extracted with ether (6×300 ml). The insoluble solid material was extracted by stirring in ether (4×1 L) for 2 h. The combined ether extracts were dried over MgSO4, filtered and concentrated to give 4 as a colourless oil (24 g, 73%), which crystallised on standing. Spectral data for this sample were consistent with those given in the literature2. 1H NMR (200 MHz, d6-DMSO) 6.45 (d, J=8.4 Hz, 1H), 4.57 (t,J=5.6 Hz, 1H), 4.35 (t,J=5.1 Hz, 1H), 3.40 (m, 4H), 3.23 (m, 1H), 1.62 (m, 1H), 1.40 (m, 1H), 1.36 (s, 9H); 13C NMR (50 MHz, d6-DMSO) 155.5, 77.4, 63.5, 58.0, 49.6, 34.4, 2.83.

Workup

  1. customThe cooling bath was removed when the reaction
  2. temperaturethe reaction mixture was heated slowly
  3. temperatureto reflux for 1 h
  4. customconsumption of the starting material
  5. customthe lumps formed
  6. customto give a slurry that
  7. filtrationThe mixture was filtered
  8. concentrationthe filtrate concentrated in vacuum to ca. 100 ml
  9. extractionwas extracted with ether (6×300 ml)
  10. extractionThe insoluble solid material was extracted
  11. dry with materialThe combined ether extracts were dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-3b79428001464944bcf8d1524bb45f3c
Source dataset
uspto-grants-2002_10
Patent number
US06472533B1

Reaction notes

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