Diisopropylamine → (2R,3R)-2-butyl-3-hydroxyoctanoic acid t-butyl ester

HRID 1695165Notes

Reaction equation

HRID 1695165 reaction equation
C(NC(C)C)(C)C.C[Li].[C:10]([O:14][C:15](=[O:24])[CH2:16][C@H:17]([OH:23])[CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])([CH3:13])([CH3:12])[CH3:11].I[CH2:26][CH2:27][CH2:28][CH3:29].[Cl-].[NH4+]>CN(C)P(=O)(N(C)C)N(C)C.C(OCC)C>[C:10]([O:14][C:15](=[O:24])[C@H:16]([CH2:26][CH2:27][CH2:28][CH3:29])[C@H:17]([OH:23])[CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])([CH3:11])([CH3:13])[CH3:12]

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 10962Butyl iodideHCID 25517Ammonium ChlorideHCID 86645801(R)-3-hydroxyoctanoic acid t-butyl esterHCID 178418348HCID 178418348, compound

Product 1

HCID 86645802(2R,3R)-2-butyl-3-hydroxyoctanoic acid t-butyl esterYield 44.9%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
-78 °C

Procedure

A dried two-necked flask was cooled to −78° C., after which diisopropylamine (5.41 g, 53.5 mmol) was introduced thereto. Then, methyllithium (a 0.98M diethyl ether solution, 45 ml, 44.1 mmol) was added dropwise thereto, and stirred for 10 minutes. The resulting mixture was heated to 0° C., and stirred for another 30 minutes. The reaction solution was cooled to −48° C., the (R)-3-hydroxyoctanoic acid t-butyl ester (3.50 g, 16.2 mmol) obtained in Production Example B-1 was added dropwise thereto, and then the mixture was stirred for 30 minutes. To the obtained mixture was added hexamethylphosphoric triamide (HMPA) (7 ml), the mixture was stirred for one minute, then 1-iodobutane (3.87 g, 21.0 mmol) was added dropwise thereto. After the reaction solution was stirred at −48° C. for one hour, a saturated ammonium chloride solution was added thereto, and extracted 3 times with diethyl ether. The resulting organic layer was dried with anhydrous magnesium sulfate, filtered, and condensed. The obtained residue was purified by column chromatography (silica gel: 150 g, n-hexane/ethyl acetate=15/1) to produce the target compound (1.98 g, 44%).

Workup

  1. temperatureThe resulting mixture was heated to 0° C.
  2. stirringstirred for another 30 minutes
  3. temperatureThe reaction solution was cooled to −48° C.
  4. additionwas added dropwise
  5. stirringthe mixture was stirred for 30 minutes
  6. stirringthe mixture was stirred for one minute
  7. stirringAfter the reaction solution was stirred at −48° C. for one hour
  8. extractionextracted 3 times with diethyl ether
  9. dry with materialThe resulting organic layer was dried with anhydrous magnesium sulfate
  10. filtrationfiltered
  11. customcondensed
  12. customThe obtained residue was purified by column chromatography (silica gel: 150 g, n-hexane/ethyl acetate=15/1)

Sources & evidence

ORD record
ord-98396e532fb14ca49ccbadc800e54602
Source dataset
uspto-grants-2012_04
Patent number
US08163713B2

Reaction notes

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