1-Bromo-4-(dimethoxymethyl)benzene → HCID 57142883, compound

HRID 1264305Notes

Reaction equation

HRID 1264305 reaction equation
[CH3:1][O:2][CH:3]([O:11][CH3:12])[C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][CH:5]=1.C([Li])CCC.[Si:18]([O:35][C:36]1[N:41]=[CH:40][CH:39]=[CH:38][N:37]=1)([C:31]([CH3:34])([CH3:33])[CH3:32])([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C1COCC1.CCOCC.[Cl-].[Cl-].[Zn+2].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][O:2][CH:3]([O:11][CH3:12])[C:4]1[CH:9]=[CH:8][C:7]([C:39]2[CH:40]=[N:41][C:36]([O:35][Si:18]([C:31]([CH3:34])([CH3:33])[CH3:32])([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[N:37][CH:38]=2)=[CH:6][CH:5]=1

Participants

8

Reactant 3

HCID 6883421-Bromo-4-(dimethoxymethyl)benzeneHCID 86588998HCID 86588998, compoundHCID 178418339Butyllithium

Product 1

HCID 57142883HCID 57142883, compoundYield 47%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled (−78° C.) solution of 4-bromo-benzaldehyde dimethyl ketal (2.31 g 10 mmol) in THF (30 mL) is added, dropwise, n-butyl lithium (4.4 mL, 2.5 M in hexanes). On complete addition, the reaction mixture is stirred for 5 min then ZnCl2 solution (20 mL, 0.5M in THF) is added. The cold bath is removed and stirring continued for 5 min. then a solution comprising of 5-bromo-(2-[t-butyldiphenylsilyloxy]-pyrimidine (4.13 g, 10 mmol) and (Ph3P)4Pd (1.1 g, 1 mmol) in THF (20 mL) is added. This mixture is warmewd to 60° C. and stirred at this temperature for 2 h. The resulting solution is cooled to room temperature, diluted with ether, washed, sequentially, with 5% aqueous ammonia solution, water and brine, dried over MgSO4 and concentrated. The residue is purified by flash chromatography (eluting with 10% ethyl acetate, 10% dichloromethane in hexanes) to give 2.28 g of the title compound as an oil. 1H NMR (CDCl3) δ 1.18 (s, 9H), 3.35 (s, 6H), 5.44 (s, 1H), 7.38 (m, 6H), 7.44 (d, J=8 Hz, 2H), 7.53 (d, J=8 Hz, 2H), 7.8 (m, 4H), 8.59 (s, 2H).

Workup

  1. additionis added
  2. additionOn complete addition
  3. customThe cold bath is removed
  4. stirringstirring
  5. waitcontinued for 5 min.
  6. customis warmewd to 60° C.
  7. stirringstirred at this temperature for 2 h
  8. washwashed
  9. dry with materialsequentially, with 5% aqueous ammonia solution, water and brine, dried over MgSO4
  10. concentrationconcentrated
  11. customThe residue is purified by flash chromatography (eluting with 10% ethyl acetate, 10% dichloromethane in hexanes)

Sources & evidence

ORD record
ord-a57fa78396f24237adf30f99807f85c6
Source dataset
uspto-grants-2003_04
Patent number
US06541505B1

Reaction notes

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