Benzyl bromoacetate → HCID 10348881, compound

HRID 129868Notes

Reaction equation

HRID 129868 reaction equation
[C:1]1([N:7]2[CH2:13][CH2:12][C:11]([CH2:14][CH2:15][O:16][Si:17]([C:30]([CH3:33])([CH3:32])[CH3:31])([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:10][CH2:9][C:8]2=[O:34])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:46][C:47]([O:49][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)=[O:48]>O1CCCC1>[C:1]1([N:7]2[CH2:13][CH2:12][C:11]([CH2:14][CH2:15][O:16][Si:17]([C:30]([CH3:31])([CH3:33])[CH3:32])([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:10][CH:9]([CH2:46][C:47]([O:49][CH2:50][C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)=[O:48])[C:8]2=[O:34])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 62576Benzyl bromoacetateHCID 2733832Lithium HexamethyldisilazideHCID 10389956HCID 10389956, compound

Product 1

HCID 10348881HCID 10348881, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Compound (9) (650 mg, 1.38 mmol) was dissolved in tetrahydrofuran (5 mL) and cooled to -78° C. The resulting reaction mixture was treated with 1.8 mL of a 1M solution of lithium bis (trimethylsilyl)amide in tetrahydrofuran and stirred for 20 min. At this time, benzyl 2-bromoacetate (437 μL, 2.76 mmol) was added, the reaction continued at -78° C. for 10 rain and then warmed to room temperature (removed dry ice/isopropanol bath). After the reaction mixture reached room temperature, 10% NH4Cl (aqueous) was added and the resulting mixture was extracted with ethyl acetate. The combined organic fractions were dried over anhydrous MgSO4, filtered and evaporated at reduced pressure. The residue was purified using flash chromatography (silica gel, 4×20 cm, 20- 40% ethyl acetate/hexane) to yield the title compound (11) (388 mg, 46%). Compound (21): 1H NMR (CDCl3) δ 1.05 (9H, s), 1.98-2.73 (5H, m), 2.90-3.23 (1H, m), 3.37-3.73 (1H, m), 3.77 (2H, t, J=6.8 Hz), 4.07-4.80 (2H, m), 5.03-5.27 (3H, m), 6.97-7.83 (20H, m); MS (DCI/NH4) m/e 618 (M+H)+ ; TLC Rf 0.47 (silica gel, 7:3 hexane:ethyl acetate).

Workup

  1. customThe resulting reaction mixture
  2. customcontinued at -78° C. for 10 rain
  3. temperaturewarmed to room temperature
  4. custom(removed dry ice/isopropanol bath)
  5. customreached room temperature
  6. addition10% NH4Cl (aqueous) was added
  7. extractionthe resulting mixture was extracted with ethyl acetate
  8. dry with materialThe combined organic fractions were dried over anhydrous MgSO4
  9. filtrationfiltered
  10. customevaporated at reduced pressure
  11. customThe residue was purified

Sources & evidence

ORD record
ord-b37883adf90c41e99d54ebcd5c89fa13
Source dataset
uspto-grants-1995_11
Patent number
US05470849

Reaction notes

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