Phosphorus oxychloride → tert-butyl (2R)-2-({[7-(benzyloxy)-4-chloroquinazolin-5-yl]oxy}methyl)pyrrolidine-1-carboxylate

HRID 1442991Notes

Reaction equation

P(Cl)(Cl)([Cl:3])=O.[CH2:6]([O:13][C:14]1[CH:23]=[C:22]2[C:17]([C:18](=O)[NH:19][CH:20]=[N:21]2)=[C:16]([O:25][CH2:26][C@H:27]2[CH2:31][CH2:30][CH2:29][N:28]2[C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[CH2:6]([O:13][C:14]1[CH:23]=[C:22]2[C:17]([C:18]([Cl:3])=[N:19][CH:20]=[N:21]2)=[C:16]([O:25][CH2:26][C@H:27]2[CH2:31][CH2:30][CH2:29][N:28]2[C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Phosphorous oxychloride (520 μl) was added dropwise to a mixture of tert-butyl (2R)-2-({[7-(benzyloxy)-4-oxo-3,4-dihydroquinazolin-5-yl]oxy}methyl)pyrrolidine-1-carboxylate (500 mg) and N,N-diisopropylethylamine (52 μl) in DCM (10 ml) and the reaction mixture was heated at 50° C. for 62 hours. The reaction mixture was concentrated in vacuo and then water and saturated aqueous sodium carbonate (cooled to 4° C.) was added. The aqueous mixture was then extracted with DCM and the organic layer was dried (MgSO4) and concentrated in vacuo to leave tert-butyl (2R)-2-({[7-(benzyloxy)-4-chloroquinazolin-5-yl]oxy}methyl)pyrrolidine-1-carboxylate as a brown oil, which was used without further purification.

Workup

concentrationThe reaction mixture was concentrated in vacuo
additionwater and saturated aqueous sodium carbonate (cooled to 4° C.) was added
extractionThe aqueous mixture was then extracted with DCM
dry with materialthe organic layer was dried (MgSO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-9ff2c57bc34e489ca6ed818e187d698b
Source dataset: uspto-grants-2010_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07659279B2

Reaction notes

Loading…