Sodium Carbonate → (R)-4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine 1-oxide

HRID 75398Notes

Reaction equation

HRID 75398 reaction equation
ClC1C=CC=C(C(OO)=[O:9])C=1.[CH3:12][C@H:13]1[C:21]2[C:20]([N:22]3[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]3)=[N:19][CH:18]=[N:17][C:16]=2[CH2:15][CH2:14]1.C([O-])(O)=O.[Na+].[O-]S([O-])(=S)=O.[Na+].[Na+].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)(Cl)Cl.O>[C:31]([O:30][C:28]([N:25]1[CH2:24][CH2:23][N:22]([C:20]2[N:19]=[CH:18][N+:17]([O-:9])=[C:16]3[CH2:15][CH2:14][C@@H:13]([CH3:12])[C:21]=23)[CH2:27][CH2:26]1)=[O:29])([CH3:33])([CH3:32])[CH3:34]

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 24477Sodium ThiosulfateHCID 70297m-Chloroperbenzoic acid2×HCID 516892Sodium BicarbonateHCID 59682823(R)-tert-Butyl 4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate

Product 1

HCID 67338667(R)-4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine 1-oxideYield 100%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6212ChloroformSolvent

Procedure

Solid 77% max. m-chloroperbenzoic acid (“m-CPBA”; 23.9 g, 107 mmol) was added portionwise to a 0° C. solution of (R)-tert-butyl 4-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (20.0 g, 62.8 mmol) in CHCl3 (310 mL). The reaction mixture was stirred 5 for minutes, then warmed to room temperature and stirred for an additional 90 minutes. HPLC looked similar after 7.5 hours. The reaction mixture was cooled to 0° C., and then NaHCO3 (13.2 g, 157 mmol) and another 0.5 equivalents of m-CPBA were added. The reaction mixture was stirred overnight (14 hours). The reaction mixture was cooled to 0° C., and a solution of Na2S2O3 (29.8 g, 188 mmol) in H2O (50 mL) was added dropwise by addition funnel. This was followed by a solution of Na2CO3 (24.6 g, 232 mmol) in H2O (70 mL) by addition funnel (mixture turns homogeneous). The reaction mixture was stirred for 30 minutes, and then the mixture was extracted with CHCl3 (3×150 mL). The combined extracts were dried (Na2SO4), filtered, and concentrated to give (R)-4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine 1-oxide (21.0 g, 100%). LC/MS (APCI+) m/z 335.1 [M+H]+.

Workup

  1. stirringstirred for an additional 90 minutes
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. stirringThe reaction mixture was stirred overnight (14 hours)
  4. temperatureThe reaction mixture was cooled to 0° C.
  5. stirringThe reaction mixture was stirred for 30 minutes
  6. extractionthe mixture was extracted with CHCl3 (3×150 mL)
  7. dry with materialThe combined extracts were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-3c4a70bcba554cb98dd9a6c3a2fdb1d1
Source dataset
uspto-grants-2014_09
Patent number
US08835434B2

Reaction notes

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