Diisopropylamine → HCID 59570922, compound

HRID 2192905Notes

Reaction equation

HRID 2192905 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.CCCCCC.[Br:19][C:20]1[CH:21]=[C:22]([CH2:32][C:33]([O:35][CH3:36])=[O:34])[CH:23]=[CH:24][C:25]=1[S:26]([CH:29]1[CH2:31][CH2:30]1)(=[O:28])=[O:27].I[CH2:38][C@H:39]1[CH2:59][CH2:58][C:41]2([O:45][C@H:44]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[C@@H:43]([C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)[O:42]2)[CH2:40]1>C1COCC1.O.CN1CCCN(C)C1=O>[Br:19][C:20]1[CH:21]=[C:22]([CH:32]([CH2:38][C@H:39]2[CH2:59][CH2:58][C:41]3([O:45][C@H:44]([C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=4)[C@@H:43]([C:52]4[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=4)[O:42]3)[CH2:40]2)[C:33]([O:35][CH3:36])=[O:34])[CH:23]=[CH:24][C:25]=1[S:26]([CH:29]1[CH2:31][CH2:30]1)(=[O:28])=[O:27]

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 21051867(2R,3R,7S)-7-(iodomethyl)-2,3-diphenyl-1,4-dioxaspiro[4.4]nonaneHCID 59570968HCID 59570968, compoundHCID 178418244HCID 178418244, compound

Product 1

HCID 59570922HCID 59570922, compoundYield 72.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent2×

Conditions

Temperature
-50 °C

Procedure

To a mixture of diisopropylamine (6.94 mL), 1,3-dimethyltetrahydropyrimidin-2(1H)-one (18 mL) and THF (60 mL) was added 2.64 M n-butyl lithium/hexane solution (18.4 mL) at an internal temperature of −50° C. or lower, followed by stirring at an internal temperature of −50° C. or lower for 1 hour. To the reaction mixture was added dropwise a solution of methyl [3-bromo-4-(cyclopropylsulfonyl)phenyl]acetate (15.0 g) in THF (20 mL)/1,3-dimethyl tetrahydropyrimidin-2(1H)-one (9 mL) at an internal temperature of −50° C. or lower, followed by stirring at the same temperature for 30 minutes, and THF (30 mL) was added thereto, followed by stirring at −20° C. for 1 hour. A solution of (2R,3R,7S)-7-(iodomethyl)-2,3-diphenyl-1,4-dioxaspiro[4.4]nonane (21.8 g) in THF (20 mL) was added dropwise thereto at an internal temperature of −60° C. or lower, followed by stirring at the same temperature for 30 minutes and then stirring at room temperature overnight. To the reaction mixture was added water (200 mL) under ice-cooling, followed by extraction with ethyl acetate (100 mL×3). The organic layer was sequentially washed with water (200 mL) and saturated brine (200 mL), and dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate 19:1→1:1) to obtain methyl 2-[3-bromo-4-(cyclopropylsulfonyl)phenyl]-3-[(2R,3R,7R)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl]propionate (20.4 g) as a pale yellow amorphous substance.

Workup

  1. stirringby stirring at the same temperature for 30 minutes
  2. stirringby stirring at −20° C. for 1 hour
  3. customat an internal temperature of −60° C.
  4. stirringby stirring at the same temperature for 30 minutes
  5. stirringstirring at room temperature overnight
  6. temperaturecooling
  7. extractionfollowed by extraction with ethyl acetate (100 mL×3)
  8. washThe organic layer was sequentially washed with water (200 mL) and saturated brine (200 mL)
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customthe solvent was then evaporated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate 19:1→1:1)

Sources & evidence

ORD record
ord-e55b5d05d6a84117b7cdb1da02edc2c4
Source dataset
uspto-grants-2012_12
Patent number
US08329707B2

Reaction notes

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