Acetic Acid → HCID 66805280, compound

HRID 1193257Notes

Reaction equation

HRID 1193257 reaction equation
C(O)(=O)C.Cl.[NH2:6][C@H:7]1[C:15]2[C:10](=[CH:11][C:12]([C:17]([O:19][CH3:20])=[O:18])=[C:13]([F:16])[CH:14]=2)[CH2:9][CH2:8]1.[CH3:21][C:22]([CH3:24])=O.[BH4-].[Na+]>CO>[F:16][C:13]1[CH:14]=[C:15]2[C:10]([CH2:9][CH2:8][C@H:7]2[NH:6][CH:22]([CH3:24])[CH3:21])=[CH:11][C:12]=1[C:17]([O:19][CH3:20])=[O:18]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 180AcetoneHCID 4311764Sodium borohydrideHCID 66798889HCID 66798889, compound

Product 1

HCID 66805280HCID 66805280, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Glacial acetic acid (0.33 ml) was added to a mixture of (R)-methyl 1-amino-6-fluoro-2,3-dihydro-1H-indene-5-carboxylate hydrochloride (A-05) [see above] (4.1 g, 19.6 mmol, 1 eq) and acetone (28.8 ml, 392.3 mmol, 20 eq) in methanol (100 ml), and the reaction mixture was stirred for 3 h at room temperature. It was then cooled to 0° C. and NaBH4 (2.23 g, 58.8 mmol, 3 eq) was added in portions. Stirring was carried out for a further 2 h at room temperature. After monitoring by TLC, concentration was carried out under reduced pressure and the residue was diluted with water (100 ml). Extraction with dichloromethane (150 ml) was carried out and the organic phase was washed with sat. sodium hydrogen carbonate solution (100 ml) and dried over sodium sulfate. The solvent was distilled off under reduced pressure and then the crude product was purified by column chromatography (Alox, 10% ethyl acetate/hexane) to yield the desired product in the form of a light-brown liquid. Yield: 76% (3.75 g, 19.61 mmol)

Workup

  1. temperatureIt was then cooled to 0° C.
  2. stirringStirring
  3. waitwas carried out for a further 2 h at room temperature
  4. concentrationAfter monitoring by TLC, concentration
  5. additionthe residue was diluted with water (100 ml)
  6. extractionExtraction with dichloromethane (150 ml)
  7. washthe organic phase was washed with sat. sodium hydrogen carbonate solution (100 ml)
  8. dry with materialdried over sodium sulfate
  9. distillationThe solvent was distilled off under reduced pressure
  10. customthe crude product was purified by column chromatography (Alox, 10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-b8bf1a92d2af45669707a8091987e541
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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