(2-Iodoethoxy)triisopropylsilane → (5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-3-(2-(triisopropylsilyloxy)ethyl)piperidin-2-one

HRID 1048269Notes

Reaction equation

HRID 1048269 reaction equation
[CH2:1]([C@H:4]1[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([CH2:24][CH:25]2[CH2:27][CH2:26]2)[C:5]1=[O:28])[CH:2]=[CH2:3].I[CH2:30][CH2:31][O:32][Si:33]([CH:40]([CH3:42])[CH3:41])([CH:37]([CH3:39])[CH3:38])[CH:34]([CH3:36])[CH3:35]>>[CH2:1]([C:4]1([CH2:30][CH2:31][O:32][Si:33]([CH:37]([CH3:38])[CH3:39])([CH:34]([CH3:36])[CH3:35])[CH:40]([CH3:41])[CH3:42])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([CH2:24][CH:25]2[CH2:27][CH2:26]2)[C:5]1=[O:28])[CH:2]=[CH2:3]

Participants

3

Reactant 2

HCID 11450272(2-Iodoethoxy)triisopropylsilaneHCID 60154122(3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)piperidin-2-one

Product 1

HCID 58573657(5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-3-(2-(triisopropylsilyloxy)ethyl)piperidin-2-one

Conditions

Temperature
40 °C

Procedure

To a solution of 3.70 g (8.9 mmol) of a mixture of C-3 diastereomers of (5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)piperidin-2-oneoxopentanoate (Example 35, Step B) and 20.7 g (63 mmol) of (2-iodoethoxy)triisopropylsilane in dry, degassed THF (60 mL) was added 54.5 mL (54.5 mmol) of a 1 M solution of lithium bis(trimethylsilyl)amide in THF slowly via syringe over 6 min. After 10 min, the orange solution was warmed to 40° C. and stirred for an additional 2.25 h. The reaction was cooled to room temperature, quenched with saturated aqueous ammonium chloride, and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by flash chromatography on silica gel (2-25% EtOAc/hexanes, gradient elution) provided the title compound (mixture of C-3 epimers) as a light yellow oil.

Workup

  1. customdegassed THF (60 mL)
  2. additionwas added 54.5 mL (54.5 mmol) of a 1 M solution of lithium bis(trimethylsilyl)amide in THF slowly via syringe over 6 min
  3. temperatureThe reaction was cooled to room temperature
  4. customquenched with saturated aqueous ammonium chloride
  5. extractionextracted with EtOAc (3×)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated
  9. customPurification of the residue by flash chromatography on silica gel (2-25% EtOAc/hexanes, gradient elution)

Sources & evidence

ORD record
ord-72fd4d468f5843ab8c7810a5ef4ff562
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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