HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

Toluene → (R)-4-chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine-5-oxide

HRID 243639
Notes
Print preview

Reaction equation

HRID 243639 reaction equation
C1([C@@H](C(C2C=CC=CC=2)O)[OH:8])C=CC=CC=1.C1(C)C=CC=CC=1.[Cl:24][C:25]1[C:26]2[S:46][CH2:45][CH2:44][C:27]=2[N:28]=[C:29]([N:31]2[CH2:36][CH2:35][N:34]([C:37]3[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][CH:38]=3)[CH2:33][CH2:32]2)[N:30]=1.CC(OO)(C)C>O>[Cl:24][C:25]1[C:26]2[S@:46](=[O:8])[CH2:45][CH2:44][C:27]=2[N:28]=[C:29]([N:31]2[CH2:32][CH2:33][N:34]([C:37]3[CH:38]=[CH:39][C:40]([Cl:43])=[CH:41][CH:42]=3)[CH2:35][CH2:36]2)[N:30]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 1140TolueneHCID 6410tert-Butyl hydroperoxideHCID 594759174-Chloro-2-[4-(4-chlorophenyl)piperazin-1-yl]-6,7-dihydrothieno[3,2-d]pyrimidineHCID 68495654(s)-Hydrobenzoin

Product 1

HCID 86645100(R)-4-chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine-5-oxideYield 88%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

Using a jacketed reactor with mechanical stirring at 400 rpm, charge (S)-Hydrobenzoin (292 mg) and toluene (50 mL), followed by Ti(i-PrO)4 (0.20 mL) and water (0.25 mL). Stir the mixture at 20° C. for 30 min. then charge 4-Chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine (3a, 5.00 g) and stir the mixture for 15 min at 20° C. before being cooling to 0° C. (it took 20 min). Charge TBHP (70% aqueous) (0.75 mL) to the reaction mixture and stir for 23 h at 0° C. Reaction reached 96% conversion and 89% ee. Quench with 5% Na2SO3 (20 mL). Separate the layers and extract the aqueous layer with dichloromethane (50 mL). Combine organic layers and wash with water (20 mL), dry (MgSO4), filter, and concentrate affording the desired sulfoxide in (4.6 g, 88% yield, 89% ee). The product may be recrystallized from THF/water (5:1) with good recovery to yield material >96% ee. NMR (400 MHz, CDCl3) δ 7.16-7.26 (m, 2H), 6.80-6.90 (m, 2H), 3.90-4.20 (m, 4H), 3.75-3.90 (m, 1H), 3.00-3.30 (m, 7H); 13C NMR (400 MHz, CDCl3) δ 177.5, 162.5, 160.7, 149.8, 129.4, 125.7, 123.9, 118.2, 49.6, 46.5, 44.7, 44.4, 33.7 (3 signals missing due to overlap); LCMS (ESI) for C16H17Cl2N4OS (M+H)+: calcd. 383.1, obsvd. 383.0.

Workup

  1. stirringStir the mixture at 20° C. for 30 min.
  2. customReaction
  3. customQuench with 5% Na2SO3 (20 mL)
  4. customSeparate the layers
  5. extractionextract the aqueous layer with dichloromethane (50 mL)
  6. washCombine organic layers and wash with water (20 mL)
  7. dry with materialdry (MgSO4)
  8. filtrationfilter
  9. concentrationconcentrate

Sources & evidence

ORD record
ord-3402bee756b44a5ba841e39881356923
Source dataset
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08653282B2

Reaction notes

Loading…

On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes