Sodium Carbonate → 6'-(2-Fluoro-5-methoxyphenyl)trispiro[cyclobutane-1,2'-chromene-4',4''-[1,3]oxazole-3',3'''-oxetan]-2''-amine

HRID 594908Notes

Reaction equation

HRID 594908 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:17]3([CH2:21][O:20][C:19]([N:22](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=[N:18]3)[C:13]3([CH2:16][O:15][CH2:14]3)[C:9]3([CH2:12][CH2:11][CH2:10]3)[O:8][C:5]2=[CH:6][CH:7]=1.[F:37][C:38]1[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][C:39]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1(C)C=CC=CC=1.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>[F:37][C:38]1[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][C:39]=1[C:2]1[CH:3]=[C:4]2[C:17]3([CH2:21][O:20][C:19]([NH2:22])=[N:18]3)[C:13]3([CH2:16][O:15][CH2:14]3)[C:9]3([CH2:10][CH2:11][CH2:12]3)[O:8][C:5]2=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 41572112-Fluoro-5-methoxyphenylboronic acidHCID 86724300Di-tert-butyl (6'-bromotrispiro[cyclobutane-1,2'-chromene-4',4''-[1,3]oxazole-3',3'''-oxetan]-2''-yl)imidodicarbonate

Product 1

HCID 900256406'-(2-Fluoro-5-methoxyphenyl)trispiro[cyclobutane-1,2'-chromene-4',4''-[1,3]oxazole-3',3'''-oxetan]-2''-amineYield 14.7%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of di-tert-butyl (6′-bromotrispiro[cyclobutane-1,2′-chromene-4′,4″-[1,3]oxazole-3′,3′″-oxetan]-2″-yl)imidodicarbonate (14.1 mg), 2-fluoro-5-methoxyphenylboronic acid (12.7 mg), PdCl2(PPh3)2 (5.3 mg) and 1M aqueous Na2CO3 (0.1 mL) in dioxane (0.4 mL) was stirred for 2 hours at 100° C. The mixture was filtered by using Chem Elut cartridges (Agilent Technologies) and washed with CHCl3. The filtrate was evaporated to give a brown oil. The oil was dissolved in toluene (0.5 mL) and to the mixture was added silicagel (neutral; 50 mg). The mixture was stirred for 1 hour at 100° C. The mixture was filtered and washed with CHCl3. The filtrate was evaporated. The residue was purified with HPLC (Column: Waters SunFire™ Prep C18 OBD™ 5 micrometer, 19×100 mm; MeOH/0.1% aqueous HCOOH 11/89 to 95/5(v/v)) and afforded 6′-(2-fluoro-5-methoxyphenyl)trispiro[cyclobutane-1,2′-chromene-4′,4″-[1,3]oxazole-3′,3′″-oxetan]-2″-amine (1.5 mg).

Workup

  1. filtrationThe mixture was filtered
  2. washwashed with CHCl3
  3. customThe filtrate was evaporated
  4. customto give a brown oil
  5. additionwas added silicagel (neutral; 50 mg)
  6. stirringThe mixture was stirred for 1 hour at 100° C
  7. filtrationThe mixture was filtered
  8. washwashed with CHCl3
  9. customThe filtrate was evaporated
  10. customThe residue was purified with HPLC (Column: Waters SunFire™ Prep C18 OBD™ 5 micrometer, 19×100 mm; MeOH/0.1% aqueous HCOOH 11/89 to 95/5(v/v)) and

Sources & evidence

ORD record
ord-94ce1aaf31ff460a87de0594c44c69d6
Source dataset
uspto-grants-2016_01
Patent number
US09242973B2

Reaction notes

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