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

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

Participants

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

extractionextracted with EtOAc
washCombined extracts were washed with brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude product was triturated in MeOH overnight
filtrationfiltered off
customdried

Sources & evidence

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

Linked notes

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