Hydrochloric Acid → HCID 67216681, compound

HRID 2036037Notes

Reaction equation

HRID 2036037 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[C@@H:10]1[N:14]2[CH:15]=[N:16][CH:17]=[C:13]2[C:12]([OH:31])([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24]C3CCCCO3)[CH:19]=2)[CH2:11]1)[C:5]#[N:6].Cl.CCOCC>CO>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[C@@H:10]1[N:14]2[CH:15]=[N:16][CH:17]=[C:13]2[C@@:12]([OH:31])([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([OH:24])[CH:19]=2)[CH2:11]1)[C:5]#[N:6]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 67215873HCID 67215873, compound

Product 1

HCID 67216681HCID 67216681, compoundYield 34.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3-fluoro-4-((5R)-7-hydroxy-7-(3-(tetrahydro-2H-pyran-2-yloxy)phenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile (1.87 g, 4.46 mmol) in anhydrous MeOH (372 ml) was added a 2M solution of hydrochloric acid in ether (9.59 ml, 19.18 mmol) at room temperature. The crude was stirred at room temperature for 2 hrs. The crude was concentrated and quenched with saturated NaHCO3. The crude was diluted in CH2Cl2 and the organic layer was washed with water, brine, dried over MgSO4, filtered, and concentrated. The crude was purified via HPLC 20%-100% MeCN/H2O to provide 510 mg of the entitled product as the major diastereomer. MS 336.0 (M+H); LCMS condition A, retention time 0.96 min. 1H NMR (400 MHz, CDCl3) δ ppm 2.90 (d, 1H), 3.22 (dd, 1H), 5.65 (d, 1H), 6.65-6.72 (m, 2H), 6.90 (s, 1H), 7.02-7.09 (m, 2H), 7.15-7.21 (m, 2H), 7.24 (s, 1H), 7.32 (dd, 2H).

Workup

  1. concentrationThe crude was concentrated
  2. customquenched with saturated NaHCO3
  3. additionThe crude was diluted in CH2Cl2
  4. washthe organic layer was washed with water, brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude was purified via HPLC 20%-100% MeCN/H2O

Sources & evidence

ORD record
ord-c380ad46fcda41fcb61dea7a5c80e5b0
Source dataset
uspto-grants-2013_11
Patent number
US08575160B2

Reaction notes

Loading…