Hydrochloric Acid → HCID 68556009, compound

HRID 420283Notes

Reaction equation

HRID 420283 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([CH:36]=[CH:37][CH:38]=1)[CH2:8][N:9]1[C@@H:17]2[C@H:12]([C@H:13]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([NH:27][C:28](=O)[CH2:29][N:30]([CH3:32])[CH3:31])=[C:23]([F:34])[CH:22]=3)[CH2:14][S:15](=[O:19])(=[O:18])[CH2:16]2)[O:11][C:10]1=[O:35])([CH3:4])([CH3:3])[CH3:2].B.C1COCC1.Cl.[OH-].[Na+]>C1COCC1.CO>[C:1]([C:5]1[CH:6]=[C:7]([CH:36]=[CH:37][CH:38]=1)[CH2:8][N:9]1[C@@H:17]2[C@H:12]([C@H:13]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([NH:27][CH2:28][CH2:29][N:30]([CH3:32])[CH3:31])=[C:23]([F:34])[CH:22]=3)[CH2:14][S:15](=[O:18])(=[O:19])[CH2:16]2)[O:11][C:10]1=[O:35])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 131729368HCID 131729368, compound

Product 1

HCID 68556009HCID 68556009, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of N-{4-[(3aR*,7S*,7aS*)-3-(3-tert-butyl-benzyl)-2,5,5-trioxo-octahydro-1-oxa-5lambda*6*-thia-3-aza-inden-7-ylmethyl]-2-fluoro-phenyl}-2-dimethylamino-acetamide (example 6a), 0.055 g, 0.1 mmol) in THF (1.1 mL) was added borane THF-complex (1M in THF, 1 mL, 1 mmol) at 25° C. The mixture was stirred for 17 h at 25° C. and afterwards 3 h at reflux. The reaction mixture was evaporated and diluted with EtOAc; ice cold aq. H2SO4 was added carefully and the organic layer was washed with water, brine, dried over Na2SO4, filtered and evaporated to leave an amorphous powder which was dissolved in MeOH (3 mL). and 2N aq. HCl (2.5 mL) and the solution was kept at 80° C. for 17 h. The colorless solution was basified with aq. NaOH and extracted with EtOAc. Organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to give the title compound as a slight brownish foam: TLC (toluene-ETA 85:15) Rf=0.30; HPLC RtA=1.91 min; ESIMS [M+H]+=532; 1H NMR (600 MHz, DMSO-d6): δ 7.39 (s, 1H), 7.33 (m, 1H), 7.28 (t, 1H), 7.13 (d, 1H), 6.9 (d, 1H), 6.82 (d, 1H), 6.72 (t, 1H), 5.51 (d, 1H), 4.40 (d, 1H), 4.22 (d, 1H), 4.11 (t, 1H), 3.67 m, 2H), 3.44 (m, 3H), 3.01 (m, 2H), 2.84 (m, 3H), 2.55 (s, 6H), 2.46 (m, 2H), 1.25 (s, 9H).

Workup

  1. temperatureat reflux
  2. customThe reaction mixture was evaporated
  3. additiondiluted with EtOAc
  4. additionice cold aq. H2SO4 was added carefully
  5. washthe organic layer was washed with water, brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customto leave an amorphous powder which
  10. extractionextracted with EtOAc
  11. washOrganic layers were washed with brine
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-933d60f9e90342b29b7db1f5ad7883fc
Source dataset
uspto-grants-2012_01
Patent number
US08093406B2

Reaction notes

Loading…