Acetic Anhydride → (5R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl acetate

HRID 529064Notes

Reaction equation

HRID 529064 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][N+:5]([O-])=[C:4]2[CH2:9][CH2:10][C@@H:11]([CH3:12])[C:3]=12.[CH3:13][C:14]([O:16]C(C)=O)=[O:15]>>[C:14]([O:16][CH:9]1[C:4]2[N:5]=[CH:6][N:7]=[C:2]([Cl:1])[C:3]=2[C@H:11]([CH3:12])[CH2:10]1)(=[O:15])[CH3:13]

Participants

3

Reactant 2

HCID 7918Acetic AnhydrideHCID 58111337(R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine 1-oxide

Product 1

HCID 58111335(5R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl acetateYield 44%

Procedure

A solution of (R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine 1-oxide (5.5 g, 30 mmol) in Ac2O (40 ml) was heated to 110° C. for 3 hours. After cooling, the acetic anhydride was evaporated under vacuum. The residue was taken up in DCM and added to a stirring cold solution of saturated NaHCO3 solution. The layers were extracted with DCM, dried over MgSO4, filtered, and concentrated. The crude black/dark brown oil was chromatographed (Biotage) eluting with 20% EtOAc/Hexane to give (5R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl acetate (3.0 g, 44%). 1H NMR (CDCl3, 400 MHz) δ 8.92 (m, 1H), 6.30-6.03 (m, 1H), 3.60-3.30 (m, 1H), 2.84 (m, 1H), 2.40-2.20 (m, 1H), 2.15 (d, J=6 Hz, 2H), 1.75 (m, 2H), 1.47 (d, J=6.8, 2H), 1.38 (d, J=7.2, 1H). MS (APCI+) [M+H]+ 227.

Workup

  1. temperatureAfter cooling
  2. customthe acetic anhydride was evaporated under vacuum
  3. additionadded to a stirring cold solution of saturated NaHCO3 solution
  4. extractionThe layers were extracted with DCM
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude black/dark brown oil was chromatographed (Biotage)
  9. washeluting with 20% EtOAc/Hexane

Sources & evidence

ORD record
ord-5b846442eda5486394fc9ea3782e70af
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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