Diisopropylamine → 3-(2,4-Bis{[2-(trimethylsilyl)ethoxy]methoxy}phenyl)-4-(bromomethyl)-7-{[2-(trimethylsilyl)ethoxy]methoxy}-2H-1-benzopyran-2-one

HRID 2214301Notes

Reaction equation

HRID 2214301 reaction equation
N(C(C)C)C(C)C.C([Li])CCC.[CH3:13][Si:14]([CH3:57])([CH3:56])[CH2:15][CH2:16][O:17][CH2:18][O:19][C:20]1[CH:25]=[C:24]([O:26][CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[CH:23]=[CH:22][C:21]=1[C:35]1[C:36](=[O:55])[O:37][C:38]2[C:43]([C:44]=1[CH3:45])=[CH:42][CH:41]=[C:40]([O:46][CH2:47][O:48][CH2:49][CH2:50][Si:51]([CH3:54])([CH3:53])[CH3:52])[CH:39]=2.[Br:58]Br.C([O-])(O)=O.[Na+].[O-]S([O-])=O.[Na+].[Na+]>CCCCCC.C1COCC1.CCOC(C)=O>[CH3:57][Si:14]([CH3:56])([CH3:13])[CH2:15][CH2:16][O:17][CH2:18][O:19][C:20]1[CH:25]=[C:24]([O:26][CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:32])([CH3:33])[CH3:34])[CH:23]=[CH:22][C:21]=1[C:35]1[C:36](=[O:55])[O:37][C:38]2[C:43]([C:44]=1[CH2:45][Br:58])=[CH:42][CH:41]=[C:40]([O:46][CH2:47][O:48][CH2:49][CH2:50][Si:51]([CH3:54])([CH3:53])[CH3:52])[CH:39]=2

Participants

10

Reactant 6

HCID 7912DiisopropylamineHCID 24408BromineHCID 24437Sodium SulfiteHCID 516892Sodium BicarbonateHCID 219592253-(2,4-Bis{[2-(trimethylsilyl)ethoxy]methoxy}phenyl)-4-methyl-7-{[2-(trimethylsilyl)ethoxy]methoxy}-2H-1-benzopyran-2-oneHCID 178418339Butyllithium

Product 1

HCID 219591903-(2,4-Bis{[2-(trimethylsilyl)ethoxy]methoxy}phenyl)-4-(bromomethyl)-7-{[2-(trimethylsilyl)ethoxy]methoxy}-2H-1-benzopyran-2-one

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

A 250 mL 3-neck round bottom flask was equipped with a magnetic stirrer, a rubber stopper and an argon inlet/outlet adapter. This vessel was charged with THF (20 mL) via syringe, iPr2NH (1.8 mL, 14.0 mmol) via syringe and cooled to −10° C. in an ice/methanol bath. n-Butyl lithium (1.85 M (titrated) via syringe, 6.3 mL, 11.7 mmol) in hexane was added dropwise via syringe at −10° C., stirred for 15 min at −10° C. To the solution was added 3-[2,4-bis-(2-trimethylsilanyl-ethoxymethoxy)-phenyl]-4-methyl-7-(2-trimethylsilanyl-ethoxymethoxy)-chromen-2-one (5.1 g, 7.8 mol) in THF (20 mL) drop-wise via syringe. The mixture was stirred at −10° C. for 2.5 h. This mixture was added dropwise via syringe to a solution of Br2 (0.76 mL, 2 eq) in −78° C. THF (100 mL) via syringe that was contained in a 1-L 3-neck round bottom flask equipped with mechanical stirrer and septum under N2. After the addition was complete, the mixture was stirred for 5 min at −78° C. and then diluted with EtOAc (0.5 L) via syringe, saturated NaHCO3 (50 mL) via syringe and saturated Na2SO3 (100 mL) via syringe. The dry ice/acetone bath was removed and the mixture was allowed to warm to room temperature while stirring. The organic phase was separated and the aqueous phase was back-extracted with EtOAc (2×0.2 L). The combined organic phase was washed with brine (2×0.5 L) and concentrated in vacuo to yield the title compound as a crude semi-solid.

Workup

  1. customA 250 mL 3-neck round bottom flask was equipped with a magnetic stirrer
  2. stirringThe mixture was stirred at −10° C. for 2.5 h
  3. customequipped with mechanical stirrer
  4. additionAfter the addition
  5. stirringthe mixture was stirred for 5 min at −78° C.
  6. customThe dry ice/acetone bath was removed
  7. temperatureto warm to room temperature
  8. stirringwhile stirring
  9. customThe organic phase was separated
  10. extractionthe aqueous phase was back-extracted with EtOAc (2×0.2 L)
  11. washThe combined organic phase was washed with brine (2×0.5 L)
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-60747728741941919f84120b83d4b67a
Source dataset
uspto-grants-2006_09
Patent number
US07105679B2

Reaction notes

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