Diisopropylamine → HCID 54124725, compound

HRID 636002Notes

Reaction equation

HRID 636002 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[OH:13][C@H:14]([CH2:20][CH2:21][CH3:22])[CH2:15][C:16]([O:18][CH3:19])=[O:17].Br[CH2:24][C:25]([CH3:27])=[CH2:26]>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C>[CH3:26][C:25](=[CH2:24])[CH2:27][C@H:15]([C@H:14]([OH:13])[CH2:20][CH2:21][CH3:22])[C:16]([O:18][CH3:19])=[O:17]

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 3577853-Bromo-2-methyl-1-propeneHCID 13617479HCID 13617479, compoundHCID 178418339Butyllithium

Product 1

HCID 54124725HCID 54124725, compoundYield 55.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 12679HexamethylphosphoramideSolvent

Procedure

To a stirred solution of diisopropylamine (19.4 mL, 139 mmol) in 70 mL of THF at −78° C. is added dropwise 86.6 mL (139 mmol) of 1.6 M n-butyllithium in hexanes over 15 min. After 1 h, a solution of methyl (3R)-3-hydroxyhexanoate (9.2 g, 63 mmol) in 10 mL of THF is added dropwise over several minutes. The reaction mixture is stirred 1 h, then treated with a solution of 3-bromo-2-methyl-1-propene (7.6 mL, 75.6 mmol) in 10 mL of HMPA and is allowed to stand at −20° C. overnight. The reaction mixture is poured into ice-cold 1 N hydrochloric acid (300 mL) and extracted with two 200-mL portions of EtOAc. The combined organic layers are washed with two 100-mL portions of saturated aqueous sodium chloride, dried over sodium sulfate, and filtered. The solvents are removed under reduced pressure. Purification by flash chromatography on silica gel eluting with 10% EtOAc-hexanes affords 7 g (55%) of methyl (2R,3R)-2-(2-methyl-2-propene-1-yl)-3-hydroxyhexanoate as an oil.

Workup

  1. waitto stand at −20° C. overnight
  2. extractionextracted with two 200-mL portions of EtOAc
  3. washThe combined organic layers are washed with two 100-mL portions of saturated aqueous sodium chloride
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customThe solvents are removed under reduced pressure
  7. customPurification by flash chromatography on silica gel eluting with 10% EtOAc-hexanes

Sources & evidence

ORD record
ord-d7e037a0fdab4e069836cbe2e7a042e2
Source dataset
uspto-grants-2001_02
Patent number
US06191150B1

Reaction notes

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