Water → 7-(3-Carboxypropyl)-9-(hydroxymethyl)-9H-fluorene-4-carboxylic acid

HRID 1402632Notes

Reaction equation

HRID 1402632 reaction equation
[CH:1]([CH:3]1[C:15]2[CH:14]=[CH:13][CH:12]=[C:11]([C:16]([OH:18])=[O:17])[C:10]=2[C:9]2[C:4]1=[CH:5][C:6]([CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])=[CH:7][CH:8]=2)=[O:2].[BH4-].[Na+].O>CO>[OH:2][CH2:1][CH:3]1[C:15]2[CH:14]=[CH:13][CH:12]=[C:11]([C:16]([OH:18])=[O:17])[C:10]=2[C:9]2[C:4]1=[CH:5][C:6]([CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])=[CH:7][CH:8]=2

Participants

5

Reactant 3

HCID 962WaterHCID 4311764Sodium borohydride2×HCID 587760137-(3-Carboxypropyl)-9-formyl-9H-fluorene-4-carboxylic acid

Product 1

HCID 587760407-(3-Carboxypropyl)-9-(hydroxymethyl)-9H-fluorene-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In an argon-purged flask, crude 9-formyl-7-(3-carboxy-propyl)-4-fluorenecarboxylic acid (4.0 g, 0.0123 mol) was dissolved in anhydrous methanol (50 mL). The flask was placed in a room temperature bath and sodium borohydride (2.3 g, 0.0615 mol) was carefully added to the reaction in portions (Caution! Flammable gas evolution.). The reaction was stirred for two hours and another portion of sodium borohydride was added (1.2 g, 0.031 mol). After another six hours the reaction was treated with a small amount of water. The organic solvent was partially removed at reduced pressure and the mixture was acidified with concentrated HCl. Brine was added and the product was twice extracted with ethyl acetate (300 mL and 100 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and evaporated to dryness. The crude product (3.3 g, 83%) was purified by flash chromatography: silica gel 60 Å eluted with 50:50:2 ethyl acetate/chloroform/glacial acetic acid. The purified product was an orange solid (1.7 g, 43%). 1H-NMR (CD3OD): δ (ppm) 8.3 (d, 1H, Ar); 7.8 (m, 2H, Ar); 7.6 (s, 1H, Ar); 7.4 (t, 1H, Ar); 7.2 (m, 1H, Ar); 4.0 (m, 2H, CH2); 3.9 (m, 1H, CH); 2.8 (t, 2H, CH2); 2.4 (t, 2H, CH2); 2.0 (m, 2H, CH2).

Workup

  1. customIn an argon-purged flask
  2. customwas placed in a room temperature
  3. customThe organic solvent was partially removed at reduced pressure
  4. additionBrine was added
  5. extractionthe product was twice extracted with ethyl acetate (300 mL and 100 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customThe crude product (3.3 g, 83%) was purified by flash chromatography
  11. washsilica gel 60 Å eluted with 50:50:2 ethyl acetate/chloroform/glacial acetic acid

Sources & evidence

ORD record
ord-9a9ec21f5465408da57be719b53287cc
Source dataset
uspto-grants-2014_12
Patent number
US08911718B2

Reaction notes

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