Triphenylphosphine → Ammonium Hydroxide

HRID 335851Notes

Reaction equation

HRID 335851 reaction equation
FC(F)(F)S(O[C:7]1[CH:20]=[C:19]2[C:10]([O:11][C:12]3[CH:13]=[CH:14][C:15]([C:26]4[C:27]([F:32])=[N:28][CH:29]=[CH:30][CH:31]=4)=[CH:16][C:17]=3[C@:18]32[CH2:24][O:23][C:22]([NH2:25])=[N:21]3)=[C:9]([F:33])[CH:8]=1)(=O)=[O:4].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl-].[Li+].C([Sn](CCCC)(CCCC)/[CH:62]=[CH:63]/[C:64]1([CH3:68])[CH2:67][O:66][CH2:65]1)CCC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C=O)C>[NH4+:21].[OH-:4].[F:33][C:9]1[C:10]2[O:11][C:12]3[C:17](=[CH:16][C:15]([C:26]4[C:27]([F:32])=[N:28][CH:29]=[CH:30][CH:31]=4)=[CH:14][CH:13]=3)[C@@:18]3([CH2:24][O:23][C:22]([NH2:25])=[N:21]3)[C:19]=2[CH:20]=[C:7](/[CH:62]=[CH:63]/[C:64]2([CH3:68])[CH2:67][O:66][CH2:65]2)[CH:8]=1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 433294Lithium ChlorideHCID 67383011(E)-tributyl(2-(3-methyloxetan-3-yl)vinyl)stannaneHCID 86640722(S)-2-amino-5'-fluoro-2'-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthene]-7'-yl trifluoromethanesulfonate

Product 2

HCID 14923Ammonium HydroxideHCID 67383212(S,E)-4'-fluoro-7'-(2-fluoropyridin-3-yl)-2'-(2-(3-methyloxetan-3-yl)vinyl)-5H-spiro[oxazole-4,9'-xanthen]-2-amine

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A glass microwave reaction vessel was charged with (S)-2-amino-5′-fluoro-2′-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthene]-7′-yl trifluoromethanesulfonate (120 mg, 0.234 mmol), trans-dichlorobis(triphenyl-phosphine)palladium (19.69 mg, 0.028 mmol), triphenylphosphine (36.8 mg, 0.140 mmol), lithium chloride (0.041 mL, 1.987 mmol) and (E)-tributyl(2-(3-methyloxetan-3-yl)vinyl)stannane (136 mg, 0.351 mmol). DMF (2.5 mL) was added and the reaction mixture was purged with argon for several minutes. The vessel was sealed and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 120° C. for 10 mins. The mixture was cooled to rt and portioned between saturated KF (7 mL) and CH2Cl2 (20 mL). The organics were washed with brine, dried over sodium sulfate filtered and concentrated. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g; 0-50% ethyl acetate in hexanes then 50% CH2Cl2: MeOH: NH4OH in EtOAc) to provide (S,E)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-(2-(3-methyloxetan-3-yl)vinyl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine as light-yellow solid. MS m/z=462.2 [M+H].

Workup

  1. customA glass microwave reaction vessel
  2. customthe reaction mixture was purged with argon for several minutes
  3. customThe vessel was sealed
  4. temperatureThe mixture was cooled to rt
  5. washThe organics were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was absorbed onto a plug of silica gel
  10. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (40 g

Sources & evidence

ORD record
ord-d87c05db9b0f4567aea8ac1ab71fe07e
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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