Sodium Carbonate → {1-[4-(6-Fluoro-4-oxo-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 1037155Notes

Reaction equation

HRID 1037155 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[C:6](I)[C:5]2=[O:19].[C:20]([O:24][C:25](=[O:46])[NH:26][C:27]1([C:31]2[CH:36]=[CH:35][C:34](B3OC(C)(C)C(C)(C)O3)=[CH:33][CH:32]=2)[CH2:30][CH2:29][CH2:28]1)([CH3:23])([CH3:22])[CH3:21].C(=O)([O-])[O-].[Na+].[Na+]>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.COCCOC>[C:20]([O:24][C:25](=[O:46])[NH:26][C:27]1([C:31]2[CH:32]=[CH:33][C:34]([C:6]3[C:5](=[O:19])[C:4]4[C:9](=[CH:10][CH:11]=[C:2]([F:1])[CH:3]=4)[O:8][C:7]=3[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:35][CH:36]=2)[CH2:28][CH2:29][CH2:30]1)([CH3:23])([CH3:21])[CH3:22]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 115234696-FLUORO-3-IODO-2-PHENYLCHROMEN-4-ONEHCID 58326444tert-Butyl (1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutyl)carbamate

Product 1

HCID 67067635{1-[4-(6-Fluoro-4-oxo-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterYield 30.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
125 °C

Procedure

To a microwave vial were added 6-fluoro-3-iodo-2-phenyl-chromen-4-one (55 mg, 0.15 mmol), {1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (62 mg, 0.165 mmol, prepared as described in WO2008/070016), sodium carbonate solution (2M in water, 0.26 mL, 0.53 mmol), tetrakis(triphenylphosphine)palladium(0) (17 mg, 0.015 mmol) and DME (3 mL). The reaction mixture was purged using argon and heated in a microwave reactor to 125° C. for 30 min. The mixture was partitioned between water (2 mL) and EtOAc (3 mL). The aqueous phase was extracted with ethyl acetate (3 mL). The combined organic extracts were washed with brine (5 mL), dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 30% ethyl acetate in cyclohexane) to afford the title compound (22 mg, 30%). 1H NMR (400 MHz, CDCl3): δ 7.95-7.90 (m, 1H), 7.57-7.52 (m, 1H), 7.46-7.30 (m, 6H), 7.28-7.22 (m, 2H), 7.21-7.16 (m, 2H), 5.03 (s, 1H), 2.64-2.31 (m, 4H), 2.14-2.00 (m, 1H), 1.89-1.77 (m, 1H), 1.48-1.18 (m, 9H).

Workup

  1. customThe reaction mixture was purged
  2. customThe mixture was partitioned between water (2 mL) and EtOAc (3 mL)
  3. extractionThe aqueous phase was extracted with ethyl acetate (3 mL)
  4. washThe combined organic extracts were washed with brine (5 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1c4726337eb541d9ac95977277263d58
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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