Water → (2S,3S,5S)-5-amino-2-(N-((5-isoxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane

HRID 1080970Notes

Reaction equation

HRID 1080970 reaction equation
[NH2:1][C@H:2]([C@@H:10]([OH:21])[CH2:11][C@@H:12]([NH2:20])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C1(OB(O)O)C=CC=CC=1.O.C1C([N+]([O-])=O)=CC=C([O:42][C:43]([O:45][CH2:46][C:47]2[O:51][N:50]=[CH:49][CH:48]=2)=O)C=1>C1(C)C=CC=CC=1.C1COCC1>[NH2:20][C@@H:12]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:11][C@H:10]([OH:21])[C@@H:2]([NH:1][C:43]([O:45][CH2:46][C:47]1[O:51][N:50]=[CH:49][CH:48]=1)=[O:42])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 962WaterHCID 78412Phenyl dihydrogen orthoborateHCID 10085299(2S,3S,5S)-2,5-Diamino-1,6-diphenylhexan-3-OLHCID 18939817((5-Isoxazolyl)methyl)-(4-nitrophenyl)carbonate

Product 1

HCID 57164722(2S,3S,5S)-5-amino-2-(N-((5-isoxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

A mixture of 1.54 g (5.41 mmol) of (2S,3S,5S)-2,5-diamino-1,6-diphenyl-3-hydroxyhexane and 0.673 g (5.41 mmol) of phenylboric acid in anhydrous toluene (130 mL) was heated at reflux under argon for 2 hrs with removal of H2O by a Dean-Stark trap. The resulting yellow solution was allowed to cool and the solvent was removed in vacuo to give an oil which solidified upon standing. The residue was taken up in 90 ml of THF, cooled to -40° C., and treated dropwise under Ar atmosphere over a period of 1 h with 1.11 g (3.78 mmol) of ((5-isoxazolyl)methyl)-(4-nitrophenyl)carbonate in 40 ml of THF. The solution was allowed to warm to -20° C. over the next 0.5 hr, then was stirred at 0° C. for 2.5 hrs and at room temperature for 1 hr. After removal of the solvent in vacuo, the residue was taken up in ethyl acetate (200 mL), washed sequentially with 5% aqueous K2CO3 (4×25 mL) and saturated brine (25 mL), dried over Na2SO4 and concentrated in vacuo. Silica gel chromatography of the residue using a gradient of methanol in chloroform (2%, 4%, 6%) afforded a mixture of the desired product and its regioisomer. Purification of the mixture on two consecutive 250 g SiO2 columns (deactivated with 1% isopropylamine/CH2Cl2) with a gradient of isopropylamine/CH2Cl2 (0.5%, 1%) afforded the desired compound as a sticky solid (0.730 g, 1.78 mmol, 33%): 1H NMR (DMSO-d6) δ 1.17-1.57 (m, 5H), 2.56-2.69 (m, 2H), 2.75-2.86 (m, 1H), 2.89-3.00 (m, 2H), 3.53-3.71 (m, 3H), 5.06 (s, 2H), 6.32 (d, J=2.4 Hz, 1H), 7.11-7.30 (m, 10H), 8.54 (d, J2.4 Hz, 1 H). Mass spectrum: (M+H)+ =410.

Workup

  1. temperaturewas heated
  2. temperatureto cool
  3. customthe solvent was removed in vacuo
  4. customto give an oil which
  5. temperatureto warm to -20° C. over the next 0.5 hr
  6. customAfter removal of the solvent in vacuo
  7. washwashed sequentially with 5% aqueous K2CO3 (4×25 mL) and saturated brine (25 mL)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customafforded

Sources & evidence

ORD record
ord-09efd7851d964468862d6afce1d7e9e8
Source dataset
uspto-grants-1996_12
Patent number
US05583233

Reaction notes

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