Trifluoroacetic acid → 9-(4-chlorothiazol-2-yl)-5-(3-fluorophenyl)-7-(hydroxymethyl)-1,3-dimethyl-8,9-dihydro-1H-pyrimido[4,5-a]pyrrolizine-2,4(3H,7H)-dione

HRID 2201262Notes

Reaction equation

HRID 2201262 reaction equation
FC(F)(F)C(O)=O.[Si]([O:15][CH2:16][CH:17]1[CH2:24][CH:23]([C:25]2[S:26][CH:27]=[C:28]([Cl:30])[N:29]=2)[C:22]2[N:18]1[C:19]([C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[CH:40]=1)=[C:20]1[C:34](=[O:35])[N:33]([CH3:36])[C:32](=[O:37])[N:31]([CH3:38])[C:21]1=2)(C(C)(C)C)(C)C>CO.O>[Cl:30][C:28]1[N:29]=[C:25]([CH:23]2[C:22]3[N:18]([C:19]([C:39]4[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[CH:40]=4)=[C:20]4[C:34](=[O:35])[N:33]([CH3:36])[C:32](=[O:37])[N:31]([CH3:38])[C:21]4=3)[CH:17]([CH2:16][OH:15])[CH2:24]2)[S:26][CH:27]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 867235027-(((tert-Butyldimethylsilyl)oxy)methyl)-9-(4-chlorothiazol-2-yl)-5-(3-fluorophenyl)-1,3-dimethyl-8,9-dihydro-1H-pyrimido[4,5-a]pyrrolizine-2,4(3H,7H)-dione

Product 1

HCID 771076329-(4-chlorothiazol-2-yl)-5-(3-fluorophenyl)-7-(hydroxymethyl)-1,3-dimethyl-8,9-dihydro-1H-pyrimido[4,5-a]pyrrolizine-2,4(3H,7H)-dione

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

Trifluoroacetic acid (2 mL, 26.0 mmol) was added to a solution of 7-(((tert-butyldimethylsilyl)oxy)methyl)-9-(4-chlorothiazol-2-yl)-5-(3-fluorophenyl)-1,3-dimethyl-8,9-dihydro-1H-pyrimido[4,5-a]pyrrolizine-2,4(3H,7H)-dione (570 mg, 0.991 mmol) in methanol (20 mL) and water (3 mL). The mixture stirred at room temperature 20 mins. Further portions of water (1 mL) and trifluoroacetic acid (1 mL) were added and the mixture stirred for a further 3 hours. The reaction was quenched with saturated NaHCO3(aq) and extracted with chloroform (3×). The combined organic extracts were passed through a hydrophobic frit and evaporated under vacuum. Purification by chromatography on silica, eluting with 0-100% EtOAc/hexane afforded the title compounds as a mixture of diastereomers.

Workup

  1. stirringthe mixture stirred for a further 3 hours
  2. customThe reaction was quenched with saturated NaHCO3(aq)
  3. extractionextracted with chloroform (3×)
  4. customevaporated under vacuum
  5. customPurification by chromatography on silica
  6. washeluting with 0-100% EtOAc/hexane

Sources & evidence

ORD record
ord-2be1fd51d0eb446d9e04afea55e85d65
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Reaction notes

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