Formaldehyde → HCID 131720339, compound

HRID 2295180Notes

Reaction equation

HRID 2295180 reaction equation
[NH:1]([C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21])[C@H:2]([C:6]([NH:8][C@H:9]([C:17]([OH:19])=[O:18])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])[CH:3]([CH3:5])[CH3:4].C=O.O.[C:33]1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1C=CC=CC=1>[CH3:4][CH:3]([CH3:5])[CH:2]([NH:1][C:20](=[O:21])[O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:6]([N:8]1[CH:9]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:17](=[O:19])[O:18][CH2:33]1)=[O:7]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 521998p-Toluenesulfonic acid monohydrateHCID 3034056N-Benzyloxycarbonyl-valyl-phenylalanine methyl ester

Product 1

HCID 131720339HCID 131720339, compoundYield 187.4%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

Cbz-Val-Phe-OH (4.67 g, 11.7 mmol, obtained from Sigma Chemical Company, St. Louis, Mo. 63178) is combined with paraformaldehyde (5 g) and p-toluenesulfonic acid monohydrate (500 mg, 2.6 mmol) in benzene (120 mL). The reaction is heated at reflux for 23 hours with continuous removal of water with a Dean-Stark trap. The reaction then cooled to room temperature and concentrated under vacuum. The residue is dissolved in ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate (60 ) is added with mixing. The layers are then separated and the aqueous layer is extracted with ethyl acetate (2×50 mL). The organic layer and organic extracts are combined and dried over anhydrous magnesium sulfate, passed through a short pad of silica gel and the filtrate is concentrated under vacuum. The residue is then purified by flash chromatography (hexane/ethyl acetate, 95:5 to 90:10 to 80:20, silica gel) to provide [S-(R*,R*)]-[2-methyl-1-[[5-oxo-4-(phenylmethyl)-3-oxazolidinyl]carbonyl]propyl]-carbamic acid, phenylmethyl ester (2.00 g, 42%) as a foam; [α]20D +113.95 (c 0.55, CHCl3); IR (CHCl3) 3314, 3032, 2934, 1804, 1714, 1659, 1437, 1233 cm-1 ; MS m/z 411 (M+H+), 367, 268, 234, 206, 178, 162, 91.

Workup

  1. temperatureThe reaction is heated
  2. customThe reaction
  3. concentrationconcentrated under vacuum
  4. dissolutionThe residue is dissolved in ethyl acetate (100 mL)
  5. additionsaturated aqueous sodium bicarbonate (60 ) is added
  6. additionwith mixing
  7. customThe layers are then separated
  8. extractionthe aqueous layer is extracted with ethyl acetate (2×50 mL)
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationthe filtrate is concentrated under vacuum
  11. customThe residue is then purified by flash chromatography (hexane/ethyl acetate, 95:5 to 90:10 to 80:20, silica gel)

Sources & evidence

ORD record
ord-8f957d6a0c8a4db49a78078367c17d0d
Source dataset
uspto-grants-1997_11
Patent number
US05691368

Reaction notes

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