Ethyl Acetate → (S,E)-(2-((tert-butyldimethylsilyloxy)methyl)-4-(prop-1-enyl)-2,3-dihydro-1H-pyrrol-1-yl)(5-methoxy-2-nitro-4-(triisopropylsilyloxy)phenyl)methanone

HRID 513357

Reaction equation

HRID 513357 reaction equation
FC(F)(F)S(O[C:7]1[CH2:11][C@@H:10]([CH2:12][O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[N:9]([C:21](=[O:44])[C:22]2[CH:27]=[C:26]([O:28][CH3:29])[C:25]([O:30][Si:31]([CH:38]([CH3:40])[CH3:39])([CH:35]([CH3:37])[CH3:36])[CH:32]([CH3:34])[CH3:33])=[CH:24][C:23]=2[N+:41]([O-:43])=[O:42])[CH:8]=1)(=O)=O.[CH:47](/B(O)O)=[CH:48]\[CH3:49].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(OCC)(=O)C>O1CCOCC1.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.O>[Si:14]([O:13][CH2:12][C@@H:10]1[CH2:11][C:7](/[CH:47]=[CH:48]/[CH3:49])=[CH:8][N:9]1[C:21]([C:22]1[CH:27]=[C:26]([O:28][CH3:29])[C:25]([O:30][Si:31]([CH:32]([CH3:34])[CH3:33])([CH:38]([CH3:39])[CH3:40])[CH:35]([CH3:36])[CH3:37])=[CH:24][C:23]=1[N+:41]([O-:43])=[O:42])=[O:44])([C:17]([CH3:18])([CH3:19])[CH3:20])([CH3:16])[CH3:15]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 62657Potassium Phosphate, TribasicHCID 6157276((1E)-prop-1-en-1-yl)boronic acidHCID 71550534(S)-5-((tert-butyldimethylsilyloxy)methyl)-1-(5-methoxy-2-nitro-4-(triisopropylsilyloxy)benzoyl)-4,5-dihydro-1H-pyrrol-3-yl trifluoromethanesulfonate

Product 1

HCID 86717761(S,E)-(2-((tert-butyldimethylsilyloxy)methyl)-4-(prop-1-enyl)-2,3-dihydro-1H-pyrrol-1-yl)(5-methoxy-2-nitro-4-(triisopropylsilyloxy)phenyl)methanoneYield 70%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
25 °C

Procedure

Tetrakis(triphenylphosphine)palladium(0) (0.41 g, 0.35 mmol, 0.03 eq) was added to a mixture of the triflate 5 (8.4 g, 11.8 mmol, 1.0 eq), E-1-propene-1-ylboronic acid (1.42 g, 16.5 mmol, 1.4 eq) and potassium phosphate (5.0 g, 23.6 mmol, 2.0 eq) in dry dioxane (60 mL) under a nitrogen atmosphere. The mixture was stirred at 25° C. for 120 mins when LC/MS indicated complete reaction. Ethyl acetate (120 mL) and water (120 mL) were added, the organic phase was removed, washed with brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, 95/5 v/v n-hexane/EtOAc to 90/10 v/v n-hexane/EtOAc) to afford the product as a yellow foam (4.96 g, 70%). LC/MS (4.477 min (ES+)), m/z: 605.0 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 7.67 (s, 1H), 6.74 (s, 1H), 5.93 (d, 1H, J=15.4 Hz), 5.67 (s, 1H), 4.65 (m, 1H), 4.04 (m, 2H), 3.86 (s, 3H), 2.85 (m, 1H), 2.71 (m, 1H), 1.72 (dd, 3H, J=6.8, 1.0 Hz), 1.30-1.22 (m, 3H), 1.07 (d, 18H, J=7.2 Hz), 0.87 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H).

Workup

  1. customreaction
  2. customthe organic phase was removed
  3. washwashed with brine (20 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography (silica gel, 95/5 v/v n-hexane/EtOAc to 90/10 v/v n-hexane/EtOAc)

Sources & evidence

ORD record
ord-cfcd74d726c74eb38d09f8c8a8256876
Source dataset
uspto-grants-2015_08
Patent number
US09102704B2

Linked notes

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