Diisopropylamine → (4S)-2'-(cyclopropylethynyl)-7'-(2,2-dimethylpropoxy)spiro[1,3-oxazole-4,9'-xanthen]-2-amine

HRID 1970247Notes

Reaction equation

Br[C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([O:16][CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:9][CH:10]=3)[C@:5]3([CH2:25][O:24][C:23]([NH2:26])=[N:22]3)[C:4]=2[CH:3]=1.C(NC(C)C)(C)C.[C:34]([CH:36]1[CH2:38][CH2:37]1)#[CH:35]>CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[CH:36]1([C:34]#[C:35][C:2]2[CH:15]=[CH:14][C:13]3[O:12][C:11]4[C:6](=[CH:7][C:8]([O:16][CH2:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[CH:9][CH:10]=4)[C@:5]4([CH2:25][O:24][C:23]([NH2:26])=[N:22]4)[C:4]=3[CH:3]=2)[CH2:38][CH2:37]1

Participants

Conditions

Temperature: 50 °C

Procedure

A vial was charged with (4R)-2′-bromo-7′-(2,2-dimethylpropoxy)spiro[1,3-oxazole-4,9′-xanthen]-2-amine (52.5 mg, 126 μmol), tetrakis(triphenylphosphine)palladium(0) (14.5 mg, 12.6 μmol), copper(I) iodide (4.79 mg, 25.2 μmol), diisopropylamine (629 μl, 126 μmol), and ethynylcyclopropane (32.0 μl, 377 μmol). The vial was heated in a 50° C. oil bath for 15 h. The reaction mixture was diluted with EtOAc and filtered through celite. The filtrate was evaporated, and the crude residue was purified by chromatography on a 12-g Redi-Sep column, eluting with 0-5% MeOH/DCM to give (4S)-2′-(cyclopropylethynyl)-7′-(2,2-dimethylpropoxy)spiro[1,3-oxazole-4,9′-xanthen]-2-amine as a white solid. MS m/z=403.2 [M+H]+. Calc'd for C25H27N2O3: 403.2.

Workup

filtrationfiltered through celite
customThe filtrate was evaporated
customthe crude residue was purified by chromatography on a 12-g Redi-Sep column
washeluting with 0-5% MeOH/DCM

Sources & evidence

ORD record: ord-1eab2c36c42b45428f23c6b4221d5222
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08426447B2

Reaction notes

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