Formaldehyde → 3-[5-(benzyloxy)-2-hydroxyphenyl]-1-[(5-chloro-2-thienyl)methyl]-3-hydroxymethyl-1,3-dihydro-2H-indol-2-one

HRID 2385029Notes

Reaction equation

HRID 2385029 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([OH:32])=[C:13]([CH:15]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]([CH2:24][C:25]3[S:26][C:27]([Cl:30])=[CH:28][CH:29]=3)[C:16]2=[O:31])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:33]=[O:34].[OH-].[Na+]>O1CCCC1.O>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([OH:32])=[C:13]([C:15]2([CH2:33][OH:34])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]([CH2:24][C:25]3[S:26][C:27]([Cl:30])=[CH:28][CH:29]=3)[C:16]2=[O:31])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 673578743-[5-(benzyloxy)-2-hydroxyphenyl]-1-[(5-chlorothiophen-2-yl)methyl]-1,3-dihydro-2H-indol-2-one

Product 1

HCID 673797413-[5-(benzyloxy)-2-hydroxyphenyl]-1-[(5-chloro-2-thienyl)methyl]-3-hydroxymethyl-1,3-dihydro-2H-indol-2-oneYield 91%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 3-[5-(benzyloxy)-2-hydroxyphenyl]-1-[(5-chlorothiophen-2-yl)methyl]-1,3-dihydro-2H-indol-2-one (2.80 g, 6.07 mmol), para-formaldehyde (0.73 g, 24.3 mmol) in tetrahydrofuran (10.0 mL) was added an aqueous solution of sodium hydroxide (0.97 g, 24.3 mmol) in water (10.0 mL) at 0° C. The reaction solution was stirred for 2 h, then quenched by the addition of 10% aqueous hydrochloric acid solution (30.0 mL). The reaction mixture was extracted with ethyl acetate (3×50 mL). The combined organic solution was washed with saturated ammonium chloride (3×50 mL), brine (50.0 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was triturated with diethyl ether, filtered and dried to afford 3-[5-(benzyloxy)-2-hydroxyphenyl]-1-[(5-chlorothiphen-2-yl)methyl]-3-(hydroxymethyl)-1,3-dihydro-2H-indol-2-one (2.71 g, 91%) as a colourless solid: MS (ES+) m/z 494.2 (M+1), 492.3 (M+1).

Workup

  1. customquenched by the addition of 10% aqueous hydrochloric acid solution (30.0 mL)
  2. extractionThe reaction mixture was extracted with ethyl acetate (3×50 mL)
  3. washThe combined organic solution was washed with saturated ammonium chloride (3×50 mL), brine (50.0 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo to dryness
  7. customThe residue was triturated with diethyl ether
  8. filtrationfiltered
  9. customdried

Sources & evidence

ORD record
ord-c2e528162adc487fa6b5311167542be3
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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