Sodium Hydroxide → 5-Chloro-2-[[(2R)-2-fluoro-3-(trityloxy)propyl]oxy]benzonitrile

HRID 1160476Notes

Reaction equation

HRID 1160476 reaction equation
[F:1]C(F)(S(F)(=O)=O)C(F)(F)C(F)(F)C(F)(F)F.N12CCCN=C1CCCCC2.[Cl:29][C:30]1[CH:31]=[CH:32][C:33]([O:38][CH2:39][C@H:40](O)[CH2:41][O:42][C:43]([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[C:34]([CH:37]=1)[C:35]#[N:36].[OH-].[Na+]>C1(C)C=CC=CC=1>[Cl:29][C:30]1[CH:31]=[CH:32][C:33]([O:38][CH2:39][C@@H:40]([F:1])[CH2:41][O:42][C:43]([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[C:34]([CH:37]=1)[C:35]#[N:36]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 67814Perfluoro-1-butanesulfonyl fluorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 684202295-Chloro-2-[[(2S)-2-hydroxy-3-(trityloxy)propyl]oxy]benzonitrile

Product 1

HCID 684199965-Chloro-2-[[(2R)-2-fluoro-3-(trityloxy)propyl]oxy]benzonitrileYield 81%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
35 °C

Procedure

Perfluorobutanesulfonyl fluoride (594 g, 2.0 mol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (282 g, 1.85 mol) were added to an ice-cooled toluene (14.5 L) solution of 5-chloro-2-[[(2S)-2-hydroxy-3-(trityloxy)propyl]oxy]benzonitrile (580 g, 1.23 mol) at the same temperature in a nitrogen atmosphere, followed by stirring the reaction mixture at 35° C. Toluene (2.0 L) and a 1N sodium hydroxide aqueous solution (1.7 L) were added to the reaction mixture to separate an organic layer which was then washed 3 times each sequentially with the 1N sodium hydroxide aqueous solution (1.7 L) and water (1.1 L), followed by vacuum concentration. Methanol (3.3 L) was added to the resultant crude crystal, followed by heating the reaction mixture to 44° C. before cooling to room temperature. The precipitated crystal was filtered and then washed with methanol (0.75 L), followed by drying at 50° C. for 18 hours to obtain 470 g of the title compound (yield: 81%).

Workup

  1. customto separate an organic layer which
  2. washwas then washed 3 times each sequentially with the 1N sodium hydroxide aqueous solution (1.7 L) and water (1.1 L)
  3. concentrationfollowed by vacuum concentration
  4. additionMethanol (3.3 L) was added to the resultant crude crystal
  5. temperatureby heating the reaction mixture to 44° C.
  6. temperaturebefore cooling to room temperature
  7. filtrationThe precipitated crystal was filtered
  8. washwashed with methanol (0.75 L)
  9. customby drying at 50° C. for 18 hours

Sources & evidence

ORD record
ord-8be845b81eee40f7bf0716529cd5181d
Source dataset
uspto-grants-2010_10
Patent number
US07816405B2

Reaction notes

Loading…