Diisopropylamine → 3-tert-Butoxycarbonylamino-5-(1-hydroxy-cyclohexyl)-thiophene-2-carboxylic acid methyl ester

HRID 2099695Notes

Reaction equation

HRID 2099695 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[CH3:13][O:14][C:15]([C:17]1[S:18][CH:19]=[CH:20][C:21]=1[NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[O:16].[C:30]1(=[O:36])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1>C1COCC1>[CH3:13][O:14][C:15]([C:17]1[S:18][C:19]([C:30]2([OH:36])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)=[CH:20][C:21]=1[NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[O:16]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 7967CyclohexanoneHCID 18925408Methyl 3-[(tert-butoxycarbonyl)amino]thiophene-2-carboxylateHCID 178418339Butyllithium

Product 1

HCID 577953883-tert-Butoxycarbonylamino-5-(1-hydroxy-cyclohexyl)-thiophene-2-carboxylic acid methyl esterYield 84,253.703%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

Diisopropylamine (140 g, 1.39 mol) and 800 mL dry THF were added to a dry 12 L 4 neck flask with a mechanical stirrer under nitrogen. The solution was cooled to −40° C. and n-BuLi (1.29 mol) was added slowly while keeping the inside temperature around −40° C. The mixture was stirred for 45 min at −40° C. and then cooled to −78° C. To this solution, a solution of 3-tert-butoxycarbonylamino-thiophene-2-carboxylic acid methyl ester (99 g, 0.384 mmol) in 3.2 L THF was added drop wise. The mixture was stirred for 60 min at −78° C. and then cyclohexanone (118 g, 1.19 mmol) was added in 30 seconds. The mixture was stirred for 30 min at −78° C. The reaction mixture was quenched with 0.75 L of NH4Cl (sat). The aqueous phase was extract with 0.75 L of EtOAc. Combined the organic phase and washed them with 5 L of brine, Dried over Na2SO4, filtered and evaporated to a residue to afford 115 g (84%) of 3-tert-Butoxycarbonylamino-5-(1-hydroxy-cyclohexyl)-thiophene-2-carboxylic acid methyl ester.

Workup

  1. customthe inside temperature around −40° C
  2. temperaturecooled to −78° C
  3. stirringThe mixture was stirred for 60 min at −78° C.
  4. stirringThe mixture was stirred for 30 min at −78° C
  5. customThe reaction mixture was quenched with 0.75 L of NH4Cl (sat)
  6. extractionThe aqueous phase was extract with 0.75 L of EtOAc
  7. washwashed them with 5 L of brine
  8. dry with materialDried over Na2SO4
  9. filtrationfiltered
  10. customevaporated to a residue

Sources & evidence

ORD record
ord-37a15ad1aaa34285b9ae9ccf599a9f64
Source dataset
uspto-grants-2009_08
Patent number
US07569600B2

Reaction notes

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