Methanol → HCID 90702916, compound

HRID 719378Notes

Reaction equation

HRID 719378 reaction equation
[CH2:1]([O:8][N:9]=[CH:10][CH2:11][C@@H:12]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:13]([O:15][CH3:16])=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.C([BH3-])#N.[Na+].C(ON)C1C=CC=CC=1>C1(C)C=CC(S(O)(=O)=O)=CC=1.C(OCC)(=O)C.C(OCC)(=O)C.CCCCCCC.O>[CH2:1]([O:8][NH:9][CH2:10][CH2:11][C@@H:12]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:13]([O:15][CH3:16])=[O:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 887MethanolHCID 102313O-BenzylhydroxylamineHCID 5003444Sodium cyanoborohydrideHCID 91389230HCID 91389230, compound

Product 1

HCID 90702916HCID 90702916, compoundYield 49.1%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6101p-Toluenesulfonic acidSolvent2×HCID 8857Ethyl AcetateSolventHCID 21899848Ethylacetate heptaneSolvent

Conditions

Temperature
22 °C

Procedure

J1) To a stirred solution of methyl (2R)-4-[(benzyloxy)imino]-2-[(tert-butoxycarbonyl)-amino]butanoate (1.7 g, 5.0 mmoles) and dry methanol (50 mL) was added sodium cyanoborohydride (0.31 g, 5.0 mmoles) followed dropwise addition of a 1M solution of 4-toluenesulfonic acid (N.B. crystal water present in commercial 4-toluenesulfonic acid has to be removed by azeotropic evaporation with benzene or toluene prior to use) in dry methanol at such a rate so as to keep pH of the mixture at 3–4 (moist indicator paper). After stirring at 22° C. for 2.5 hours TLC and LC indicated a complete reaction. The methanol was stripped off by rotary evaporation leaving a white solid which was taken up in ethyl acetate (100 mL), washed with saturated sodium bicarbonate solution and brine and dried over anhydrous sodium sulfate. Filtration and concentration by rotary evaporation gave 1.7 g of a crude which was chromato-graphed on silica with ethyl acetate/n-heptane (1:5 through 1:3) as eluents. To rid the product from traces of O-benzylhydroxylamine it was chromatographed once more on silica using dichloromethane and dichloromethane/methanol (98:2) as eluents to afford 0.83 g (49% yield) of the subtitle compound as a colourless oil. MS (APCI) m/z 339 (M+1). 1H NMR (CDCl3) δ 7.40–7.27 (m, 5H), 5.47 (br d, J=8 Hz, 1H), 4.74 (s, 2 H), 4.41–4.31 (m, 1H), 3.72 (s, 3H), 3.10–2.93 (m, 2H), 2.20–2.05 (m, 1H), 1.88–1.78 (m, 1H) and 1.43 (s, 9H) ppm.

Workup

  1. customto be removed by azeotropic evaporation with benzene or toluene
  2. customa complete reaction
  3. customThe methanol was stripped off by rotary evaporation
  4. customleaving a white solid which
  5. washwashed with saturated sodium bicarbonate solution and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationFiltration and concentration
  8. customby rotary evaporation
  9. customgave 1.7 g of a crude which
  10. customwas chromatographed once more on silica

Sources & evidence

ORD record
ord-5a814125cc6a4f4cae7ced7182207d29
Source dataset
uspto-grants-2006_11
Patent number
US07132434B2

Reaction notes

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