Ethanol → ethyl (2S*,3R*)-2-(dibenzylamino)-3-hydroxy-4-methyl-pentanoate

HRID 530562Notes

Reaction equation

HRID 530562 reaction equation
[CH2:1]([N:8]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C@@H:9]([C:15](=[O:18])[CH2:16][CH3:17])[C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH4+].[Cl-].[BH4-].[Na+].[CH3:30]CO>O>[CH2:19]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C@@H:9]([C@H:15]([OH:18])[CH:16]([CH3:30])[CH3:17])[C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 86699979ethyl (2S*)-2-(dibenzylamino)-3-oxo-pentanoate

Product 1

HCID 86700006ethyl (2S*,3R*)-2-(dibenzylamino)-3-hydroxy-4-methyl-pentanoateYield 48%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred solution of ethyl (2S*)-2-(dibenzylamino)-3-oxo-pentanoate [prepared as for example 47, step 1] (2.76 g, 7.8 mmol) in EtOH (90 mL), at rt, a solution of NH4Cl (8.34 g, 156 mmol) in H2O (23 mL) was added. NaBH4 (2.95 g, 78 mmol) was then added in small portions. After 1 h from the last addition, the reaction was quenched with H2O and the solvent evaporated. The crude mixture was taken up with H2O and CH2Cl2 and pH corrected to 9 with 20% NH4OH aqueous solution. After extraction, the organic phase was dried over Na2SO4, filtered, and concentrated in vacuo to give a crude product, as an oil. Purification by column chromatography using a Teledyne ISCO apparatus, eluting with Cy:AcOEt (90:10), gave the title compound (1.33 g, 48% over 2 steps), as a pure syn diastereoisomer, as a colorless oil. MS (ESI) m/z: 356 [M−H]+. 1H NMR (DMSO-d6) δ 0.66 (d, J=6.69 Hz, 3H), 0.71 (d, J=6.68 Hz, 3H), 1.26 (t, J=7.09 Hz, 3H), 1.66 (h, J=6.63 Hz, 1H), 3.24 (d, J=7.12 Hz, 1H), 3.63 (d, J=13.94 Hz, 2H), 3.63 (m, 1H) 4.06 (d, J=14.06 Hz, 2H), 4.10-4.27 (m, 2H), 4.61 (d, J=4.60 Hz, 1H), 7.15-7.45 (m, 10H).

Workup

  1. additionAfter 1 h from the last addition
  2. customthe reaction was quenched with H2O
  3. customthe solvent evaporated
  4. extractionAfter extraction
  5. dry with materialthe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a crude product
  9. customPurification by column chromatography
  10. washeluting with Cy

Sources & evidence

ORD record
ord-55ba84d3eed147dcbe2987ee93bf06c6
Source dataset
uspto-grants-2016_05
Patent number
US09353075B2

Reaction notes

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