Ammonium Chloride → Benzyl 2(S)-tert-butoxycarbonylamino-4(R)-hydroxy-5-nitropentanoate

HRID 269604Notes

Reaction equation

HRID 269604 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:20][C:21](=[O:26])[CH2:22][N+:23]([O-:25])=[O:24])[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl-].[NH4+]>O1CCCC1>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:20][C@@H:21]([OH:26])[CH2:22][N+:23]([O-:25])=[O:24])[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 25517Ammonium ChlorideHCID 57481716Benzyl 2(S)-tert-butoxycarbonylamino-5-nitro-4-oxopentanoate

Product 1

HCID 57481715Benzyl 2(S)-tert-butoxycarbonylamino-4(R)-hydroxy-5-nitropentanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 11.3 g (30.8 mmol) of benzyl 2(S)-tert-butoxycarbonylamino-5-nitro-4-oxopentanoate in 300 ml of tetrahydrofuran is cooled to −78° C., 30.8 ml of a 1M solution of L-Selectrideo in tetrahydrofuran are added dropwise, and the mixture is stirred at −78° C. for 1 h. After warming to RT, a saturated ammonium chloride solution is cautiously added to the solution. The reaction solution is concentrated, and the residue is taken up in water and ethyl acetate. The aqueous phase is extracted three times with ethyl acetate. The combined organic phases are dried over sodium sulfate and evaporated. The crude product is prepurified on silica gel 60 (mobile phase: cyclohexane/ethyl acetate 10/1), and the collected fractions are concentrated and stirred with cyclohexane/ethyl acetate 5/1. The remaining crystals are collected by suction filtration and dried. 2.34 g (21% of theory) of the desired diastereomer are obtained. Chromatographic separation of the mother liquor on Lichrospher Diol 10 μm (mobile phase: ethanol/isohexane 5/95) results in a further 0.8 g (6.7% of theory) of the product.

Workup

  1. temperatureAfter warming to RT
  2. concentrationThe reaction solution is concentrated
  3. extractionThe aqueous phase is extracted three times with ethyl acetate
  4. dry with materialThe combined organic phases are dried over sodium sulfate
  5. customevaporated
  6. concentrationthe collected fractions are concentrated
  7. stirringstirred with cyclohexane/ethyl acetate 5/1
  8. filtrationThe remaining crystals are collected by suction filtration
  9. customdried
  10. custom2.34 g (21% of theory) of the desired diastereomer are obtained
  11. customChromatographic separation of the mother liquor on Lichrospher Diol 10 μm (mobile phase: ethanol/isohexane 5/95)
  12. customresults in a further 0.8 g (6.7% of theory) of the product

Sources & evidence

ORD record
ord-a7c7d0dbd8eb4f40b13348fc21d0bbc8
Source dataset
uspto-grants-2008_11
Patent number
US07446102B2

Reaction notes

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