Isopropylamine → Tert-butyl 2-(8-fluoroisoquinolin-5-yl)acetate

HRID 1519874Notes

Reaction equation

C(N)(C)C.[Li]CCCC.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1.[C:38]([O:42][C:43](=[O:45])[CH3:44])([CH3:41])([CH3:40])[CH3:39].Br[C:47]1[CH:56]=[CH:55][C:54]([F:57])=[C:53]2[C:48]=1[CH:49]=[CH:50][N:51]=[CH:52]2>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:57][C:54]1[CH:55]=[CH:56][C:47]([CH2:44][C:43]([O:42][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:45])=[C:48]2[C:53]=1[CH:52]=[N:51][CH:50]=[CH:49]2

Participants

Conditions

Temperature: 23 °C

Procedure

A 30 mL reaction vial was flame dried and charged with isopropylamine (0.67 mL, 4.8 mmol) in toluene (3 mL). The solution was chilled to 0° C. before a 1.5M solution of nBuLi (4.8 mmol, 3.2 mL) was added. Pd2(dba)3 catalyst (184 mg, 0.2 mmol) was added, followed by ligand 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (160 mg, 0.4 mmol), and t-butylacetate (464 mg, 4 mmol). After 15 min, a toluene (3 mL) solution of 5-bromo-8-fluoroisoquinoline (200 mg, 0.9 mmol) was added. The reaction was stirred for 16 h while warming to 23° C. The crude mixture was purified by column chromatography (3% MeOH/DCM) to give tert-butyl 2-(8-fluoroisoquinolin-5-yl)acetate (140 mg). LCMS showed an m/z of 262.1 with a retention time of 1.469 min, method [1].

Workup

customA 30 mL reaction
temperaturevial was flame
customdried
additionwas added
customThe crude mixture was purified by column chromatography (3% MeOH/DCM)

Sources & evidence

ORD record: ord-05526c8cf8fc4bceac9ee14b05ebceb8
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073891B2

Reaction notes

Loading…