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Cesium carbonate → (3aR,6aR)-3-(6-Chloro-2-morpholinopyrimidin-4-yl)tetrahydrofuro[3,4-d]oxazol-2(3H)-one

HRID 538924
Notes
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Reaction equation

HRID 538924 reaction equation
[O:1]1[C@H:5]2[CH2:6][O:7][CH2:8][C@H:4]2[NH:3][C:2]1=[O:9].[Cl:10][C:11]1[CH:16]=[C:15](Cl)[N:14]=[C:13]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:12]=1.C([O-])([O-])=O.[Cs+].[Cs+].C([O-])(O)=O.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[Ar]>[Cl:10][C:11]1[N:12]=[C:13]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:14]=[C:15]([N:3]2[C@@H:4]3[CH2:8][O:7][CH2:6][C@@H:5]3[O:1][C:2]2=[O:9])[CH:16]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 27720684-(4,6-Dichloropyrimidin-2-yl)morpholineHCID 55303430(3aR,6aR)-tetrahydrofuro[3,4-d]oxazol-2(3H)-one

Product 1

HCID 86694354(3aR,6aR)-3-(6-Chloro-2-morpholinopyrimidin-4-yl)tetrahydrofuro[3,4-d]oxazol-2(3H)-oneYield 88.6%

Reagents, catalysts & solvents

3
HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 86694355Argon 4,5-bis(diphenylphosphino)-9,9-dimethylxantheneCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of (3aR,6aR)-tetrahydrofuro[3,4-d]oxazol-2(3H)-one (500 mg, 3.87 mmol), 4-(4,6-dichloropyrimidin-2-yl)morpholine (1088 mg, 4.65 mmol) and Cs2CO3 (2.14 g, 6.58 mmol) in dioxane (20 mL) was added after degassing with argon 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (157 mg, 0.271 mmol) and Pd2(dba)3 (70.9 mg, 0.077 mmol) and the reaction mixture was heated for 6 h at 85° C. The reaction mixture was added to 10% aqueous NaHCO3 solution and extracted with EtOAc. Combined extracts were washed with brine, dried over MgSO4, filtered and concentrated. The crude product was triturated in MeOH overnight, filtered off and dried to afford the title compound as a colorless solid (1.12 g, 87%): tR=0.92 min (LC-MS 3); ESI-MS: 327, 329 [M+H]+ (LC-MS 3).

Workup

  1. extractionextracted with EtOAc
  2. washCombined extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was triturated in MeOH overnight
  7. filtrationfiltered off
  8. customdried

Sources & evidence

ORD record
ord-bda22b43dbb34821baabd86acef054a1
Source dataset
uspto-grants-2014_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08865894B2

Reaction notes

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