Benzyl Bromide → HCID 70049710, compound

HRID 1584413Notes

Reaction equation

HRID 1584413 reaction equation
[CH:1]([NH:4][CH:5]([CH3:7])[CH3:6])([CH3:3])[CH3:2].[CH3:8][O:9][C:10]([C:12]1([CH2:18][S:19]([C:22]2[CH:27]=[CH:26][C:25]([O:28][C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=3)=[CH:24][CH:23]=2)(=[O:21])=[O:20])[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)=[O:11].C([N-]C(C)C)(C)C.[Li+:43].[CH2:44](Br)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>O1CCCC1.Cl>[CH:1]([N-:4][CH:5]([CH3:7])[CH3:6])([CH3:3])[CH3:2].[Li+:43].[CH3:8][O:9][C:10]([C:12]1([CH2:18][S:19]([C:22]2[CH:27]=[CH:26][C:25]([O:28][C:29]3[CH:30]=[CH:31][C:32]([Cl:35])=[CH:33][CH:34]=3)=[CH:24][CH:23]=2)(=[O:20])=[O:21])[CH2:17][CH2:16][O:15][CH2:14][CH:13]1[CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:11]

Participants

8

Reactant 4

HCID 7498Benzyl BromideHCID 7912DiisopropylamineHCID 2724682Lithium diisopropylamideHCID 70050250HCID 70050250, compound

Product 2

HCID 2724682Lithium diisopropylamideHCID 70049710HCID 70049710, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Lithium diisopropylamide was prepared by the addition of 2.5M N-butyl lithium (610 μL, 1.53 mmol) in hexanes to a solution of diisopropylamine (200 μL, 1.53 mmol) in tetrahydrofuran (3 mL) at 0° C. and stirring for 20 minutes. Then a solution of 4-[4-(4-chlorophenoxy)phenylsulfonylmethyl]-tetrahydropyran-4-carboxylic acid methyl ester (540 mg, 1.27 mmol) in tetrahydrofuran (1 mL) was added to the solution of lithium diisopropylamide at -78° C., and stirred for an additional 60 minutes. Benzyl bromide (181 μL, 1.53 mmol) of was added to the mixture, stirred for an 50 minutes, warmed to room temperature over 30 minutes, and stirred for an additional 3 hours. The mixture was then diluted with 0.1M aqueous hydrochloric acid (25 mL) and extracted with methylene chloride (2×50 mL). The combined organic layers were dried over magnesium sulfate, concentrated in vacuo, chromatographed over silica gel, eluted with 20% ethyl acetate/hexanes, to afford 3-benzyl-4-[4-(4-chlorophenoxy)phenylsulfonylmethyl]-tetrahydropyran-4-carboxylic acid methyl ester (440 mg, 67%) . IR (KBr) 1736 cm-1 ; 1HNMR (CDCl3) δ 1.78 (dm, J=13.5 Hz, 1H), 2.02-2.17 (m, 2H), 2.39 (dm, J=13.5 Hz, 1H), 3.19-3.23 (m, 2H), 3.37-3.45 (td, J=11.9, 2.4 Hz, 2H), 3.77-3.85 (m, 1H), 3.84 (s, 3H), 3.88-3.98 (m, 2H), 4.07-4.17 (m, 2H), 6.83-6.90 (m, 4H), 6.94 (d, J=8.7 Hz, 2H), 7.08-7.15 (m, 3H), 7.37 (d, J=8.7 Hz, 2H), 7.62 (d, J=8.7 Hz, 2H); FABMS (M+ +H): 515.

Workup

  1. stirringstirred for an additional 60 minutes
  2. stirringstirred for an 50 minutes
  3. stirringstirred for an additional 3 hours
  4. extractionextracted with methylene chloride (2×50 mL)
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customchromatographed over silica gel
  8. washeluted with 20% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-be41a1096e9b484bbb5d5deea41c6e3a
Source dataset
uspto-grants-1999_08
Patent number
US05932595

Reaction notes

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