Tetramethyltin → tert-butyl N-(4-{2-[4-methyl-4-(trifluoromethoxy)biphenyl-3-yl]ethyl}benzoyl)-beta-alaninate

HRID 1880597Notes

Reaction equation

HRID 1880597 reaction equation
[CH3:1][Sn](C)(C)C.Br[C:7]1([O:39][C:40]([F:43])([F:42])[F:41])[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:9][CH:8]1[CH2:19][CH2:20][C:21]1[CH:38]=[CH:37][C:24]([C:25]([NH:27][CH2:28][CH2:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:26])=[CH:23][CH:22]=1>CN(C=O)C.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>[CH3:1][C:7]1([O:39][C:40]([F:43])([F:42])[F:41])[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:9][CH:8]1[CH2:19][CH2:20][C:21]1[CH:38]=[CH:37][C:24]([C:25]([NH:27][CH2:28][CH2:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:26])=[CH:23][CH:22]=1

Participants

5

Reactant 2

HCID 11661TetramethyltinHCID 86761706Tert-butyl N-(4-{2-[4-bromo-4-(trifluoromethoxy)biphenyl-3-yl]ethyl}benzoyl)-beta-alaninate

Product 1

HCID 86761705tert-butyl N-(4-{2-[4-methyl-4-(trifluoromethoxy)biphenyl-3-yl]ethyl}benzoyl)-beta-alaninate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

Tetramethylstannane (41 μl, 0.295 mmol) was added to the intermediate from Example 1 Step H (35 mg, 0.059 mmol), Pd(PPh3)4 (5 mg, 0.04 mmol) in 3 mL DMF. The solution was then heated at 120° C. overnight under an argon atmosphere. The solution was cooled and partitioned between ethyl acetate and water. The organic phase was washed with water (3×) and brine. The solution was then dried over Na2SO4, filtered and concentrated. The residue was purified by PTLC using 6/4 hexanes/ethyl acetate mobile phase to give tert-butyl N-(4-{2-[4-methyl-4-(trifluoromethoxy)biphenyl-3-yl]ethyl}benzoyl)-β-alaninate. The tert butyl group was removed with TFA as described in EXAMPLE 1 Step I to give the title compound. 1H NMR (500 MHz, CDCl3): δ 7.73 (d, J=7.9 Hz, 2H); 7.54 (d, J=8.5 Hz, 2H); 7.36-7.33 (m, 1H); 7.31-7.23 (m, 6H); 6.81-6.76 (m, 1H); 3.80-3.75 (m, 2H); 2.99 (s, 4H); 2.77 (t, J=5.7 Hz, 2H); 2.35 (s, 3H). LCMS1 3.94 min (M+H)=472

Workup

  1. temperatureThe solution was cooled
  2. custompartitioned between ethyl acetate and water
  3. washThe organic phase was washed with water (3×) and brine
  4. dry with materialThe solution was then dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by PTLC

Sources & evidence

ORD record
ord-eae074f1ad1c43af8751656d77ec47be
Source dataset
uspto-grants-2012_11
Patent number
US08318760B2

Reaction notes

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