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

HRID 1970250Notes

Reaction equation

HRID 1970250 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.CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[NH:65]1[CH2:70][CH2:69][O:68][CH2:67][CH2:66]1>C1COCC1.[Cl-].[NH4+].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]>[CH3:19][C:18]([CH3:21])([CH3:20])[CH2:17][O:16][C:8]1[CH:9]=[CH:10][C:11]2[O:12][C:13]3[C:4](=[CH:3][C:2]([N:65]4[CH2:70][CH2:69][O:68][CH2:67][CH2:66]4)=[CH:15][CH:14]=3)[C@@:5]3([CH2:25][O:24][C:23]([NH2:26])=[N:22]3)[C:6]=2[CH:7]=1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 2733832Lithium HexamethyldisilazideHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 58466128(R)-2'-bromo-7'-(neopentyloxy)-5H-spiro[oxazole-4,9'-xanthen]-2-amine

Product 1

HCID 59272347(4S)-2'-(2,2-dimethylpropoxy)-7'-(4-morpholinyl)spiro[1,3-oxazole-4,9'-xanthen]-2-amine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
65 °C

Procedure

A vial was charged with (4R)-2′-bromo-7′-(2,2-dimethylpropoxy)spiro[1,3-oxazole-4,9′-xanthen]-2-amine (80.0 mg, 192 μmol), DavePhos (9.05 mg, 23.0 μmol), tris(dibenzylideneacetone)dipalladium(0) (8.78 mg, 9.59 μmol), lithium bis(trimethylsilyl)amide (767 μl of a 1.0 M solution in THF, 767 μmol), and morpholine (50.1 μl, 575 μmol). The vial was sealed and heated in a 65° C. oil bath for 15 h. The reaction mixture was diluted with a saturated aqueous ammonium chloride solution (10 mL) and extracted with DCM (3×10 mL). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue was purified by chromatography on a 12-g Redi-Sep column, eluting with 0-8% MeOH/DCM. The first fraction containing product was mixed and was discarded. The remaining fractions were combined and evaporated to yield (4S)-2′-(2,2-dimethylpropoxy)-7′-(4-morpholinyl)spiro[1,3-oxazole-4,9′-xanthen]-2-amine as a pale yellow solid. MS m/z=424.2 [M+H]+. Calc'd for C24H30N3O4: 424.2.

Workup

  1. customThe vial was sealed
  2. extractionextracted with DCM (3×10 mL)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by chromatography on a 12-g Redi-Sep column
  7. washeluting with 0-8% MeOH/DCM
  8. additionThe first fraction containing product
  9. additionwas mixed
  10. customevaporated

Sources & evidence

ORD record
ord-db5dc3c8a0db4adc836697435965e642
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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