Methanol → (6-bromo-1-hydroxy-2,3-dihydro-1H-inden-2-yl)acetic Acid

HRID 1585164Notes

Reaction equation

HRID 1585164 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH:7]([CH2:12][C:13]([OH:15])=[O:14])[C:8]2=[O:11])=[CH:4][CH:3]=1.CO.O1CCCC1.[BH4-].[Na+]>O>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH:7]([CH2:12][C:13]([OH:15])=[O:14])[CH:8]2[OH:11])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 4311764Sodium borohydride2×HCID 212218342-(6-bromo-1-oxo-2,3-dihydro-1H-inden-2-yl)acetic acid

Product 1

HCID 67104698(6-bromo-1-hydroxy-2,3-dihydro-1H-inden-2-yl)acetic Acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

6-Bromo-2-carboxymethyl-1-indanone (139 g, 650 mmol), methanol (1100 mL), and tetrahydrofuran (200 mL) were stirred at 0° C. Sodium borohydride (9.30 g, 245 mmol) was added in portions over 45 minutes and stirred another 45 minutes. More sodium borohydride (12.4 g, 326 mmol) was added in portions over 45 minutes and stirred another 60 minutes. Water was added and the solvent was removed under vacuum at 35° C. The residue was partitioned between diethyl ether and water. The organic layer was washed with water and brine and then dried over sodium sulfate. Flash chromatography of the crude product on a 30×7 cm silica gel column, eluting with dichloromethane/ethyl acetate/hexane (1:2:5), yielded an orange wax (99.6 g, 57%). 1H-NMR (300 MHz, CDCl3) (a ratio of approximately 1:1 cis to trans diastereomers) 7.55 (s, 0.43H), 7.51 (s, 0.57H), 7.39 (t, 0.57H, J=8.1), 7.39 (t, 0.43H, J=8.1), 7.13 (d, 0.43H, J=8.1), 7.08 (d, 0.57H, J=8.1), 5.44 (d, 0.57H, J=6.9), 5.30 (d, 0.43H, J=6.0), 3.79 (s, 1.71H), 3.77 (s, 1.29H), 3.45-2.95 (m, 3H), 2.87 (s, 1H).

Workup

  1. stirringstirred another 60 minutes
  2. customthe solvent was removed under vacuum at 35° C
  3. customThe residue was partitioned between diethyl ether and water
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. washFlash chromatography of the crude product on a 30×7 cm silica gel column, eluting with dichloromethane/ethyl acetate/hexane (1:2:5)
  7. customyielded an orange wax (99.6 g, 57%)

Sources & evidence

ORD record
ord-ad0a39e35e0c4f6d8fc21af49d2b85fa
Source dataset
uspto-grants-1999_08
Patent number
US05936000

Reaction notes

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