Formaldehyde → HCID 67370419, compound

HRID 1991586Notes

Reaction equation

HRID 1991586 reaction equation
[CH2:1]=[O:2].S(=O)(=O)(O)O.[CH2:8]([N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]([CH2:21][C:22]([N:24]([CH3:26])[CH3:25])=[O:23])([OH:20])[C:12]1=[O:27])[CH:9]=[CH2:10].C([O-])(=O)C.[Na+]>CC(OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=O.O.C(O)(=O)C>[CH2:8]([N:11]1[C:19]2[C:14](=[C:15]([CH3:16])[C:1]([OH:2])=[CH:17][CH:18]=2)[C:13]([CH2:21][C:22]([N:24]([CH3:25])[CH3:26])=[O:23])([OH:20])[C:12]1=[O:27])[CH:9]=[CH2:10]

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 1118Sulfuric AcidHCID 517045Sodium AcetateHCID 99705742-(1-allyl-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-N,N-dimethyl-acetamide

Product 1

HCID 67370419HCID 67370419, compoundYield 113%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 613145Acetic acid 10-acetoxymethyl-anthracen-9-ylmethyl esterSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of para-formaldehyde (36.2 g, 1.13 mol) in 150 ml of glacial acetic add, sulfuric acid (22.2 g, 0.226 mol) is added and the mixture heated at 80° C., until a clear solution has been formed. To this, during 45 minutes a solution of 2-(1-allyl-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-N,N-dimethyl-acetamide (example 26) (62 g, 226 mmol) in a mixture of glacial acetic acid (350 mL) and water (10 mL) is added. The red reaction mixture is stirred for another hour at 80° C., and by then all of the starting material is consumed (HPLC). Sodium acetate (46.3 g, 564 mmol) is added, and after stirring for 5 minutes an orange suspension forms. The solvent is removed on the rotavapor, and to the residue water (about 250 mL) is added. Extraction with chloroform (2×200 mL), drying the organic layer and removal of the solvent leaves the crude title product (77.7 g, quanta) as a red oil. After chromatographic purification white crystals, mp=125° C. 1H-NMR (CDCl3, 300 MHz) δ 2.71, 2.94 (AB, 2H, 2J=16.1 Hz, CH2CONMe2); 2.83, 2.84 (2 s, 3H each, N(CH3)2); 4.19, 4.25 (ABAllyl, 2H, 2J=16.4 Hz, 3J=5.3 Hz, NCH2); 4.47 (s, 2H, CH2OH); 5.12 (dd, 1H, 2J=1.2 Hz, 3J=10.3 Hz, cis CH═CH2), 5.51 (dd, 1H, 3J=17.3 Hz, trans CH═CH2); 5.75 (ddtr, 1H, CH═CH2); 6.21 (br s, 1H. OH); 6.70 (d, 1H, 3J=7.9 Hz, H-7); 7.15 (dd, 1H, 4J=1.5 Hz, H-6); 7.37 (d, 1H, H-4). 13C-NMR (CDCl3, 75 MHz) δ 35.71, 37.84 (N(CH3)2); 38.87 (CH2CONMe2); 42.67 (NCH2); 64.80 (CH2OH); 74.46 (C-3); 109.36 (C-7); 117.73 (CH═CH2); 123.43 (C-4); 128.63 (C-6); 131.00 (C-9); 131.33 (CH═CH2); 136.35 (C-5); 141.89 (C-8); 170.53 (C-11); 176.36 (C-2).

Workup

  1. additionadd
  2. customhas been formed
  3. additionis added
  4. customThe red reaction mixture
  5. customby then all of the starting material is consumed (HPLC)
  6. stirringafter stirring for 5 minutes an orange suspension forms
  7. customThe solvent is removed on the rotavapor
  8. additionto the residue water (about 250 mL) is added
  9. extractionExtraction with chloroform (2×200 mL)
  10. customdrying
  11. customthe organic layer and removal of the solvent

Sources & evidence

ORD record
ord-827904ba578e471c8ed08ee50ae78f05
Source dataset
uspto-grants-2010_01
Patent number
US07645886B2

Reaction notes

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