Allyl bromide → 1-(1-Tert-butoxycarbonylbut-3-enylamino)cyclohexanecarboxylic acid benzyl ester

HRID 1459891Notes

Reaction equation

HRID 1459891 reaction equation
[CH:1](NC(C)C)([CH3:3])[CH3:2].C([Li])CCC.CCCCCC.[CH2:19]([O:26][C:27]([C:29]1([NH:35][CH2:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1)=[O:28])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(Br)C=C>O1CCCC1>[CH2:19]([O:26][C:27]([C:29]1([NH:35][CH:36]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:3][CH:1]=[CH2:2])[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1)=[O:28])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

7

Reactant 5

HCID 7841Allyl bromideHCID 7912DiisopropylamineHCID 8058HexaneHCID 537423821-(Tert-butoxycarbonylmethylamino)cyclohexanecarboxylic acid benzyl esterHCID 178418339Butyllithium

Product 1

HCID 542981051-(1-Tert-butoxycarbonylbut-3-enylamino)cyclohexanecarboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

To a solution of diisopropylamine (3.03 mL, 21.6 mmol) in dry tetrahydrofuran (75 mL) at -78° C. was added a 2.38M solution of n-butyllithium in hexane (9.07 mL, 21.6 mmol). After 10 minutes, a solution of 1-(tert-butoxycarbonylmethylamino)cyclohexanecarboxylic acid benzyl ester (5.0 g, 14.4 mmol) in tetrahydrofuran (25 mL) was added and the resulting mixture was allowed to warm to -40° C. over 2.5 hours. The mixture was again cooled to -78° C. and allyl bromide was added. The mixture was allowed to warm to 0° C. over 4 hours while stirring and was quenched by addition of a saturated aqueous solution of ammonium chloride. Water was added and the mixture was extracted with ethyl acetate. The organic phase was washed with brine, dried over magnesium sulfate and evaporated under vacuum to afford an oil. The oil was chromatographed on silica gel eluting with 1% ethyl acetate in methylene chloride to give 1-(1-tert-butoxycarbonylbut-3-enylamino)cyclohexanecarboxylic acid benzyl ester as an oil, 2.0 g (36%).

Workup

  1. temperatureThe mixture was again cooled to -78° C.
  2. temperatureto warm to 0° C. over 4 hours
  3. customwas quenched by addition of a saturated aqueous solution of ammonium chloride
  4. additionWater was added
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe organic phase was washed with brine
  7. dry with materialdried over magnesium sulfate
  8. customevaporated under vacuum
  9. customto afford an oil
  10. customThe oil was chromatographed on silica gel eluting with 1% ethyl acetate in methylene chloride

Sources & evidence

ORD record
ord-753937912aa44fe8850597b1efb0c94b
Source dataset
uspto-grants-1998_12
Patent number
US05854275

Reaction notes

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