Reaction equation
CC(C)(C)OC(=O)N1CCC[C@@H](N)C1.Cc1cccnc1Br>CC(C)(C)[O-].Cc1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.O=C(/C=C/c1ccccc1)/C=C/c1ccccc1.[Na+].[Pd].[Pd].c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1>Cc1cccnc1N[C@@H]1CCCN(C(=O)OC(C)(C)C)C1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 115 °C
Procedure
Test reaction using the conditions which were shown to work in EN07957-76 2016-02-26 14:30; Pd2(DBA)3 (14 mg) and BINAP (19 mg) was stirred in toluene (2.5 ml). 14:35; 2-bromo-3-methylpyridine (344 mg), sodium t-butoxide (334 mg), and the amine (526 mg) was added to the mixture. 14:40; Heating at 115 °C. 15:10; 81% product. 15:40; 81% product, No further progress was observed, probably because of lack of amine 15:50; Another 0.4 ml amine was added to the mixture. 16:15; No further progress by HPLC, reaction terminated. 50 microlitres of the mixture was evaporated and the residue was dissolved in methanol-d4 and 1H NMR was recorded. By 1H NMR the starting pyridine was consumed completely, as opposed to the HPLC-MS which indicated 16% starting material. 2016-02-29 10:35; Purification using 25-100% ethyl acetate in heptane over 6 column lengths on a 50 g column, detection at 300 nm and collection on threshold 50 mAU. Evaporation fo the fractions gave 480 mg oil. ee measurement showed 99.9% ee
Sources & evidence
- ORD record
- ord-1fab0d514b4b411abf5f6ef0f4a2b24e
- Source dataset
- 750 AstraZeneca ELN dataset
- Original link
- View source
Linked notes
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