Diisopropylamine → HCID 178499309, compound

HRID 2099668Notes

Reaction equation

HRID 2099668 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[N:22]([C:36]([C@H:38]1[CH2:43][CH2:42][C@H:41]([CH3:44])[CH2:40][CH2:39]1)=[O:37])[C@H:23]1[CH2:28][CH2:27][C@H:26]([O:29][CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][O:31]2)[CH2:25][CH2:24]1)=[O:16].[C:45]1(=[O:51])[CH2:50][CH2:49][CH2:48][CH:47]=[CH:46]1.[NH4+].[Cl-]>C1COCC1>[CH3:13][O:14][C:15]([C:17]1[S:18][C:19]([C:45]2([OH:51])[CH2:50][CH2:49][CH2:48][CH:47]=[CH:46]2)=[CH:20][C:21]=1[N:22]([C:36]([C@H:38]1[CH2:39][CH2:40][C@H:41]([CH3:44])[CH2:42][CH2:43]1)=[O:37])[C@H:23]1[CH2:24][CH2:25][C@H:26]([O:29][CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][O:31]2)[CH2:27][CH2:28]1)=[O:16]

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 135942-Cyclohexen-1-oneHCID 25517Ammonium ChlorideHCID 178418339ButyllithiumHCID 178499316HCID 178499316, compound

Product 1

HCID 178499309HCID 178499309, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a mixture of THF (0.5 mL) and diisopropylamine (31 μl, 0.22 mmol) cooled to −40° C. n-BuLi (1.3 M, 165 μl, 0.21 mmol) was added dropwise. After stirring at this temperature for 30 min it was cooled to −78° C. and 3-{(trans-4-methyl-cyclohexanecarbonyl)-[trans-4-(tetrahydro-pyran-2-yloxy)-cyclohexyl]-amino}-thiophene-2-carboxylic acid methyl ester (82 mg, 0.18 mmol) in THF (0.5 mL) was added dropwise. The mixture was stirred at this temperature for 30 min. Cyclohex-2-enone (20 μl, 0.21 mmol) was added quickly and it was stirred for 20 min at −78° C. Saturated NH4Cl solution was added and the mixture was allowed to come to room temperature. It was extracted with EtOAc. The extract was washed with brine, dried (MgSO4) and evaporated. Pure 5-(1-hydroxy-cyclohex-2-enyl)-3-{(trans-4-methyl-cyclohexanecarbonyl)-[trans-4-(tetrahydro-pyran-2-yloxy)-cyclohexyl]-amino}-thiophene-2-carboxylic acid methyl ester was obtained after chromatography over silica gel (hexane:EtOAc—80:20 as eluent) (48 mg, 48%).

Workup

  1. additionwas added dropwise
  2. stirringThe mixture was stirred at this temperature for 30 min
  3. stirringit was stirred for 20 min at −78° C
  4. customto come to room temperature
  5. extractionIt was extracted with EtOAc
  6. washThe extract was washed with brine
  7. dry with materialdried (MgSO4)
  8. customevaporated

Sources & evidence

ORD record
ord-58f1a9e699b049018ed4e5d849632cc5
Source dataset
uspto-grants-2009_08
Patent number
US07569600B2

Reaction notes

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