3-Methoxyaniline → (S)-2-amino-4'-fluoro-7'-(3-methoxyphenylamino)-5H-spiro[oxazole-4,9'-xanthen]-2'-ol

HRID 335816Notes

Reaction equation

HRID 335816 reaction equation
[NH2:1][C:2]1[O:3][CH2:4][C@@:5]2([N:22]=1)[C:18]1[CH:17]=[C:16]([OH:19])[CH:15]=[C:14]([F:20])[C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8](Br)=[CH:9][CH:10]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.CC(C)([O-])C.[Na+].[CH3:59][O:60][C:61]1[CH:62]=[C:63]([CH:65]=[CH:66][CH:67]=1)[NH2:64]>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].C1(C)C=CC=CC=1>[NH2:1][C:2]1[O:3][CH2:4][C@@:5]2([N:22]=1)[C:18]1[CH:17]=[C:16]([OH:19])[CH:15]=[C:14]([F:20])[C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8]([NH:64][C:63]2[CH:65]=[CH:66][CH:67]=[C:61]([O:60][CH3:59])[CH:62]=2)=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 108243-MethoxyanilineHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 23676156Sodium t-butoxideHCID 58466133(S)-2-amino-7'-bromo-4'-fluoro-5H-spiro[oxazole-4,9'-xanthen]-2'-ol

Product 1

HCID 67383328(S)-2-amino-4'-fluoro-7'-(3-methoxyphenylamino)-5H-spiro[oxazole-4,9'-xanthen]-2'-olYield 51.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with (S)-2-amino-7′-bromo-4′-fluoro-5H-spiro[oxazole-4,9′-xanthen]-2′-ol (400 mg, 1.095 mmol), di-tert-butyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (81 mg, 0.192 mmol), Pd2 dba3 (50.2 mg, 0.055 mmol), sodium tert-butoxide (316 mg, 3.29 mmol) and 3-methoxyaniline (245 μL, 2.191 mmol). Toluene (2191 μL) was added and the vial was flushed with argon, sealed and shaken to combine all the components. The resulting dark mixture was heated at 100° C. for 16 hrs. The mixture was diluted with water (5 ml) and ethyl acetate (15 ml) and neutralized with saturated NH4Cl solution. The organic layer was loaded onto a 5 g SCX column and washed with EtOAc and MeOH. The material was recovered from the column by washing with 2M NH3 in MeOH. Concentration and separated by silica gel chromatography (10-80% CH2Cl2/MeOH/NH4OH in CH2CO provided (S)-2-amino-4′-fluoro-7′-(3-methoxyphenylamino)-5H-spiro[oxazole-4,9′-xanthen]-2′-ol (230 mg, 0.565 mmol, 51.5% yield). MS m/z=408.0 [M+H].

Workup

  1. customthe vial was flushed with argon
  2. customsealed
  3. additionThe mixture was diluted with water (5 ml) and ethyl acetate (15 ml)
  4. washwashed with EtOAc and MeOH
  5. customThe material was recovered from the column
  6. washby washing with 2M NH3 in MeOH
  7. concentrationConcentration
  8. customseparated by silica gel chromatography (10-80% CH2Cl2/MeOH/NH4OH in CH2CO

Sources & evidence

ORD record
ord-f239517f36494712b8a51f4b249eedcc
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

Loading…