Isopropylamine → Methyl 3-hydroxy-3-isopropyl-7-phenylheptanoate

HRID 1107144Notes

Reaction equation

HRID 1107144 reaction equation
[CH:1](N)([CH3:3])[CH3:2].[Li]CCCC.[C:10]([O:16][CH3:17])(=[O:15])[CH2:11]C(C)C.[C:18]1([CH2:24][CH2:25][CH2:26][CH2:27][CH:28]=[O:29])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C1COCC1>[OH:29][C:28]([CH:1]([CH3:3])[CH3:2])([CH2:27][CH2:26][CH2:25][CH2:24][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:11][C:10]([O:16][CH3:17])=[O:15]

Participants

6

Reactant 4

HCID 6363IsopropylamineHCID 11160Methyl isovalerateHCID 561886BenzenepentanalHCID 178418339Butyllithium

Product 1

HCID 18790185Methyl 3-hydroxy-3-isopropyl-7-phenylheptanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 2.4 mL (18.49 mmol, 1.5 eq) of isopropylamine in 50 mL of dry THF at -78° C. under argon is added 9.3 mL (14.8 mmol, 1.2 eq) of 1.6 M BuLi in hexanes solution. This is stirred at -78° C. for 1 hour at which time 1.8 mL (13.56 mmol, 1.1 eq) of methyl isovalerate is added dropwise. This mixture is stirred at -78° C. for 1.5 hours at which time 2 g (12.33 mmol) of 5-phenylpentanal in 10 mL of dry THF is added dropwise. This is stirred at -78° C. for 1 hour, then allowed to warm slowly to 0° C. over 3 hours. The reaction is quenched with saturated NH4Cl solution and then partitioned between ether and saturated NH4Cl solution. The organics are dried (Na2SO4) and concentrated in vacuo. The product is purified by flash silica gel chromatography to afford methyl 3-hydroxy-3-isopropyl-7-phenylheptanoate in the form of a yellow oil. (0.88 g, 26%): 1H-NMR (300 MHz, CDCl3) δ (TMS) 0.95(t, 6H), 1.45(m, 3H), 1.6(m, 3H), 2.08(bs, 1H), 2.15(m, 1H), 2.35(t, 1H), 2.6(t, 2H), 3.68(s, 3H), 3.85(bm, 1H), 7.15(m, 3H), 7.25(m, 2H).

Workup

  1. additionis added dropwise
  2. additionis added dropwise
  3. temperatureto warm slowly to 0° C. over 3 hours
  4. customThe reaction is quenched with saturated NH4Cl solution
  5. custompartitioned between ether and saturated NH4Cl solution
  6. dry with materialThe organics are dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe product is purified by flash silica gel chromatography

Sources & evidence

ORD record
ord-0ef565c4a07a4253b81827196914cfc3
Source dataset
uspto-grants-2000_05
Patent number
US06057369

Reaction notes

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