Sodium Chloride → HCID 44124594, compound

HRID 1692004Notes

Reaction equation

HRID 1692004 reaction equation
C[O:2][C:3]1[CH:22]=[CH:21][C:6]2[N:7]=[C:8]([N:10]3[CH2:14][CH2:13][C@@H:12]([N:15]4[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]4)[CH2:11]3)[S:9][C:5]=2[CH:4]=1.B(Br)(Br)Br.CCCCCCC.C(=O)(O)[O-].[Na+].[Cl-].[Na+]>CN(C)C=O>[N:15]1([C@@H:12]2[CH2:13][CH2:14][N:10]([C:8]3[S:9][C:5]4[CH:4]=[C:3]([OH:2])[CH:22]=[CH:21][C:6]=4[N:7]=3)[CH2:11]2)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

7

Reactant 5

HCID 5234Sodium ChlorideHCID 8900HeptaneHCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 44124593HCID 44124593, compound

Product 1

HCID 44124594HCID 44124594, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of (R)-6-methoxy-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole (Example 46) in N,N-dimethylformamide (˜0.05 M) is chilled to −78° C. under a dry nitrogen atmosphere. A 1 M solution of boron tribromide in heptane (4 equivalents) is added dropwise. When the addition is complete, the reaction mixture is allowed to warm to ambient temperature and stirring is continued for 18 hours. Ice water is carefully added to the reaction mixture and stirring is continued for 15 minutes. The pH of the reaction mixture is then adjusted to 7 by the addition of aqueous sodium bicarbonate. After rapid stirring for ten minutes, the organic layer is isolated. The aqueous layer is saturated with sodium chloride and extracted with CHCl3. The organic layers are combined, dried (MgSO4), and filtered. The filtrate is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel, eluting with 90:5:5 dichloromethane/acetonitrile/methanol. Fractions containing product are combined and concentrated under reduced pressure to give (R)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazol-6-ol.

Workup

  1. additionWhen the addition
  2. stirringstirring
  3. waitis continued for 15 minutes
  4. stirringAfter rapid stirring for ten minutes
  5. customthe organic layer is isolated
  6. extractionextracted with CHCl3
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationThe filtrate is concentrated under reduced pressure
  10. customthe residue is purified by column chromatography on silica gel
  11. washeluting with 90:5:5 dichloromethane/acetonitrile/methanol
  12. additionFractions containing product
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d8477a77b2f1423baa816ee7b36d72d4
Source dataset
uspto-grants-2012_04
Patent number
US08153813B2

Reaction notes

Loading…