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Bromide ion → 2-(1-Methyl-4-isobutylphenyl)-4-methoxymethyl-5-phenyl-2-oxazoline

HRID 6523
Notes
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Reaction equation

HRID 6523 reaction equation
[CH2:1]([C:3]1[O:4][C@@H:5]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C@H:6]([CH2:8][O:9][CH3:10])[N:7]=1)[CH3:2].C([N-][CH:21]([CH3:23])[CH3:22])(C)C.[Li+].[CH:25](NC(C)C)(C)[CH3:26].C[Li].[Br-].[Cl-].[Na+].[CH2:37]1[CH2:41]O[CH2:39][CH2:38]1>>[CH3:2][C:1]1([C:3]2[O:4][CH:5]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH:6]([CH2:8][O:9][CH3:10])[N:7]=2)[CH:26]=[CH:25][C:37]([CH2:41][CH:21]([CH3:22])[CH3:23])=[CH:38][CH2:39]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 7

HCID 259Bromide ionHCID 5234Sodium ChlorideHCID 7912DiisopropylamineHCID 8028Tetrahydrofuran4×HCID 2724682Lithium diisopropylamideHCID 10932944(4S,5S)-2-ethyl-4-methoxymethyl-5-phenyl-2-oxazoline2×
HCID 178418348
HCID 178418348, compound

Product 1

HCID 197938612-(1-Methyl-4-isobutylphenyl)-4-methoxymethyl-5-phenyl-2-oxazolineYield 90%

Procedure

A solution of the compound II (155 g, 0.71 mol) in THF (1.6 L) under nitrogen is cooled to -75° C. in a dry-ice-acetone bath. A solution of 0.8 mol of lithium diisopropylamide, derived from 98 ml of diisopropylamine and 300 ml of 2,3M butylithium (methyllithium) in 750 ml of dry THF is prepared, and added under continuous stirring in the presence of 4.0 Å molecular sieves to the solution of II in dry THF. Stirring is continued for half an hour at -75° C. and 4isobutylphenyliode (bromide) of the amount of 237.6 g (1.95 mol) in 300 ml THF (dry) is added over a period of time of 10 minutes. The resulting, colorless solution is stirred at this temperature for one hour, then subsequently permitted to reach 20° C. The reaction mixture is poured into 3L of saturated aqueous sodium chloride solution, extracted with several portions of petrolether or ether, dried over Na2SO4 or molecular sieves, (4.0 Å) and distilled in vacuo at 0.1 mm Hg to yield 90% of 2-(1-methyl-4-isobutylphenyl)-4-methoxymethyl-5-phenyl-2-oxazoline, having [α]24 -40.5° (c 10.1 in CHCl3) IR (film) 1671 cm-1, NMR (CDCl3, TMS) δ7.33 (s, 5H), 5.33 (d, J=7HZ, 1H), 4.33-3.93 (9, 1H), 3.80-3.33 (m, 2H) 3.43 (3H), 2.87-2.33 (m, 1H), and 2.00-0.68 (m, 12H).

Workup

  1. customis prepared
  2. additionadded
  3. waitis continued for half an hour at -75° C.
  4. stirringThe resulting, colorless solution is stirred at this temperature for one hour
  5. customto reach 20° C
  6. extractionextracted with several portions of petrolether or ether
  7. dry with materialdried over Na2SO4 or molecular sieves, (4.0 Å)
  8. distillationdistilled in vacuo at 0.1 mm Hg

Sources & evidence

ORD record
ord-d915f9e724c34bff918fbcf5d34e9611
Source dataset
uspto-grants-1993_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05248815

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes