3,5-Dimethylbenzyl bromide → HCID 9888665, compound

HRID 1975650Notes

Reaction equation

HRID 1975650 reaction equation
[C:1]1([CH:7]([CH:15]2[CH:20]([OH:21])[CH:19]3[CH2:22][CH2:23][N:16]2[CH2:17][CH2:18]3)[CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[Si](C)(C)[N-][Si](C)(C)C.[K+].[CH3:34][C:35]1[CH:36]=[C:37]([CH:40]=[C:41]([CH3:43])[CH:42]=1)[CH2:38]Br>>[CH3:34][C:35]1[CH:42]=[C:41]([CH2:43][O:21][CH:20]2[CH:19]3[CH2:22][CH2:23][N:16]([CH2:17][CH2:18]3)[CH:15]2[CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:40]=[C:37]([CH3:38])[CH:36]=1

Participants

4

Reactant 3

HCID 1413343,5-Dimethylbenzyl bromideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 10662535HCID 10662535, compound

Product 1

HCID 9888665HCID 9888665, compound

Procedure

To a solution of alcohol (Example 1, 0.78 g, 1:1 mixture of stereoisomers) was added 0.5M-potassium hexamethyldisilazide (5.84 ml, in toluene). After 1 h, 3,5-dimethylbenzyl bromide (0.58 g) was added for 3 h. The solution was evaporated to dryness after a further 3 h, and the residue partitioned between dichloromethan and water. The organic phase was dried (MgSO4), evaporated and purified by column chromatography on silica gel eluting with petroleum ether (bp 6014 80) containing increasing amounts of ethyl acetate (50% to 100%) and then methanol/ethyl acetate (15:85) to give a single diastereomer of the title compound. This was crystallised by addition of oxalic acid (72 mg) in propan-2-ol and diethyl ether to give 3-[(3,5-dimethylphenyl)methyloxy]-2-(1,2-diphenylethyl)-1-azabicyclo[2.2.2]octane hydrogen oxalate salt isomer A mp 64°-66° C.1HNMR(DMSO,360MHz)δ 7.2-6.6 (13H,m,aryl), 4.6 (1H, d, J=16.0 Hz, OCHAHB),4.4 (1H, d, J=16.0 Hz, OCHAHB),3.5 (1H, m, OCHCH),3.3 (1H, m, NCHAHB), 2.99 (1H, dd, NCHCH)),2.8-2.60 (5H, m, NCHAHB,NCH2,PhCH2), 2.4(1H,m,PhCHCH2),2.3 (6H, s, CH3, CH3),2.25 (1H, m, bridgehead CH),1.9 (1H, m, NCH2CHAHB),1.65 (1H, m, NCH2CHAHB), 1.46-1.22 (2H, m, NCH2CH2); Found C, 71.09; H, 6.84; N, 2.51. C30H35NO.C2H2O4.0.3H2O requires C, 71.19;H,6.86;N,2.67.m/e (EI) 425(M+), (CI+)426 (M+H), (CI-=)424 (M-H).

Workup

  1. customThe solution was evaporated to dryness after a further 3 h
  2. customthe residue partitioned between dichloromethan and water
  3. dry with materialThe organic phase was dried (MgSO4)
  4. customevaporated
  5. custompurified by column chromatography on silica gel eluting with petroleum ether (bp 6014 80)
  6. additioncontaining
  7. temperatureincreasing amounts of ethyl acetate (50% to 100%)

Sources & evidence

ORD record
ord-86a7792d7afb4fffa252b8025f4fb1cf
Source dataset
uspto-grants-1994_02
Patent number
US05288730

Reaction notes

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