Cesium carbonate → 6-Cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid

HRID 631977Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([C:13]([OH:15])=[O:14])=[N:6][C:7]=1[O:8][CH2:9][CH:10]1[CH2:12][CH2:11]1.[NH:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CO.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]>[CH:10]1([CH2:9][O:8][C:7]2[N:6]=[C:5]([C:13]([OH:15])=[O:14])[CH:4]=[CH:3][C:2]=2[N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:12][CH2:11]1

Participants

Conditions

Temperature: 95 °C

Procedure

A mixture of 5-bromo-6-(cyclopropylmethoxy)-pyridine-2-carboxylic acid (Example 9 d, 600 mg, 2 mmol), pyrrolidine (CAN 123-75-1, 1.57 g 22 mmol), tris(dibenzylidene-acetone)dipalladium (CAN 52409-22-0, 202 mg 0.2 mmol), rac-BINAP (CAN 76189-55-4, 275 mg, 0.4 mmol) and Cs2CO3 (2.88 mg 9 mmol) in toluene (50 mL) was heated to 95° C. for 20 h in a nitrogen atmosphere. Then the mixture was diluted with methanol (30 mL), filtered and the filtrate was evaporated to dryness. The residue was purified by column chromatography (silica gel, 5 g, eluting with 10% ethyl acetate in petroleum ether) to obtain the product as a white solid (0.26 g 45%), MS (LC/MS): 263.1 [M+H]+.

Workup

filtrationfiltered
customthe filtrate was evaporated to dryness
customThe residue was purified by column chromatography (silica gel, 5 g, eluting with 10% ethyl acetate in petroleum ether)

Sources & evidence

ORD record: ord-08fb417517a74a16abadaace13717eca
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321727B2

Reaction notes

Loading…