Triphenylphosphine → Tert-butyl 4-(6-bromo-2-chloro-quinazolin-8-yloxy)-piperidine-1-carboxylate

HRID 475320Notes

Reaction equation

C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C.[OH:36][CH:37]1[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38]1.[Br:50][C:51]1[CH:52]=[C:53]2[C:58](=[C:59](O)[CH:60]=1)[N:57]=[C:56]([Cl:62])[N:55]=[CH:54]2>C1COCC1.CO>[Br:50][C:51]1[CH:52]=[C:53]2[C:58](=[C:59]([O:36][CH:37]3[CH2:38][CH2:39][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:41][CH2:42]3)[CH:60]=1)[N:57]=[C:56]([Cl:62])[N:55]=[CH:54]2

Participants

Conditions

Temperature: 20 °C

Procedure

Triphenylphosphine (577 mg, 2.20 mmol), di-tert-butylazodicarboxylate (506 mg, 2.20 mmol) and tert-butyl 4-hydroxy-piperidine-1-carboxylate (1.32 g, 6.62 mmol) are taken up in 6 mL THF, stirred for 15 min at 20° C. and then combined with 6-bromo-2-chloro-quinazolin-8-ol (1.16 g, 4.45 mmol). After stirring for 24 h at 20° C. the mixture is diluted with MeOH, the solvent is eliminated in vacuo, the crude product is purified by RP-chromatography (method prep. HPLC1; 20% acetonitrile to 90% in 6 min) and tert-butyl 4-(6-bromo-2-chloro-quinazolin-8-yloxy)-piperidine-1-carboxylate (HPLC-MS: tRet.=1.99 min; method FECB5) is obtained.

Workup

stirringAfter stirring for 24 h at 20° C. the mixture
customthe crude product is purified by RP-chromatography (method prep. HPLC1; 20% acetonitrile to 90% in 6 min)

Sources & evidence

ORD record: ord-6b44ee9e45d842148e17987839f40685
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637549B2

Reaction notes

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