Ethyl Acetate → 5'-(3,5-Dimethylisoxazol-4-yl)-7'-methoxyspiro[[1,3]dioxolane-2,3'-indolin]-2'-one

HRID 1052983Notes

Reaction equation

[CH3:1][C:2]1[C:6](B(O)O)=[C:5]([CH3:10])[O:4][N:3]=1.Br[C:12]1[CH:13]=[C:14]2[C:18](=[C:19]([O:21][CH3:22])[CH:20]=1)[NH:17][C:16](=[O:23])[C:15]12[O:27][CH2:26][CH2:25][O:24]1.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>O1CCOCC1.O.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.[Cl-].[Cl-].[Fe+2].[Pd+2]>[CH3:1][C:2]1[C:6]([C:12]2[CH:13]=[C:14]3[C:18](=[C:19]([O:21][CH3:22])[CH:20]=2)[NH:17][C:16](=[O:23])[C:15]23[O:24][CH2:25][CH2:26][O:27]2)=[C:5]([CH3:10])[O:4][N:3]=1

Participants

Conditions

Temperature: 102 °C

Procedure

A mixture of 3,5-dimethylisoxazol-4-ylboronic acid (298 mg, 2.1 mmol), dichloro[1,1′-bis(di-tert-butylphosphino)ferrocene]palladium(II) (29 mg, 0.14 mmol), 5′-bromo-7′-methoxyspiro[[1,3]dioxolane-2,3′-indolin]-2′-one (210 mg, 0.7 mmol) and Na2CO3 (233 mg, 2.1 mmol) in dioxane (9 mL) and water (2 mL) was heated to 102° C. for 16 h. To the mixture was added EtOAc (50 mL), water (20 mL). The organic layer was separated and washed with water (20 mL), brine (10 mL), dried over Na2SO4, filtered and concentrated in vacuo. Purification by column chromatography, using a mixture of 33% EtOAc in dichloromethane as the eluent, to give the desired product as a light brown solid (57 mg, crude, 26%). 1H NMR (400 MHz, DMSO-d6): δH 10.62 (s, 1H), 7.02-7.03 (m, 1H), 6.92-6.93 (m, 1H), 4.26-4.34 (m, 4H), 3.86 (s, 3H), 2.38 (s, 3H), 2.10 (s, 3H). MS (ESI) m/e [M+1]+ 317.

Workup

customThe organic layer was separated
washwashed with water (20 mL), brine (10 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by column chromatography
additiona mixture of 33% EtOAc in dichloromethane as the eluent

Sources & evidence

ORD record: ord-87db68b79a084278b7e6a994bf6891a3
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09393232B2

Reaction notes

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