Ammonium Chloride → 15-(Tert-butoxy)-9-oxoprostanoic acid, ethyl ester

HRID 2420402Notes

Reaction equation

HRID 2420402 reaction equation
[Mg].[C:2]([O:6][CH:7]([CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH2:8][CH2:9]I)([CH3:5])([CH3:4])[CH3:3].[C:16]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]1[C:28](=[O:32])[CH2:29][CH2:30][CH:31]=1)([O:18][CH2:19][CH3:20])=[O:17].[Cl-].[NH4+]>C(OCC)C.O>[C:2]([O:6][CH:7]([CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH2:8][CH2:9][C@@H:31]1[C@@H:27]([CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:28](=[O:32])[CH2:29][CH2:30]1)([CH3:5])([CH3:4])[CH3:3]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 15573491Ethyl 5-oxocyclopent-1-ene-1-heptanoateHCID 204656323-tert-Butoxy-1-iodooctane

Product 1

HCID 8673293815-(Tert-butoxy)-9-oxoprostanoic acid, ethyl esterYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×

Procedure

To a Grignard solution, prepared from 5.05 g. of magnesium and 65.8 g. of 3-(tert-butoxy)-1-iodooctane in 150 ml. of diethyl ether under nitrogen atmosphere, is added 4.0 g. of copper iodide-tri-n-butylphosphine complex followed by dropwise addition of 49 g. of 2-(6-carbethoxyhexyl)cyclopent-2-en-1-one [Hardegger et al., Helv. Chim. Acta 50, 2501 (1967)] and the resulting mixture is stirred for 18 hours. Saturated ammonium chloride (110 ml.) is added followed by 100 ml. of water and 100 ml. of diethyl ether. Unreacted magnesium is removed by filtration. The ethereal layer is washed successively with aqueous sodium thiosulfate solution, ammonium chloride solution, and water, dried over magnesium sulfate and taken to dryness to give an oil. Distillation at 0.05 mm. (bath 100°-185° C.) gives 45.5 g. of material containing unreacted starting material and 30 g. (85% yield based on non-recovered starting material; see below) of residue which contains the desired product. This material is chromatographed on silica gel. The product is eluted with diethyl ether to give 25.2 g. (71% based on recovered starting material) of a syrup; this material has no significant ultraviolet absorption; λmaxKBr 5.74, 7.20, 7.35, 8.35 μ; nmr 2H quartet δ4.09 (OCH2 of ester), 1H broad singlet 3.57 (carbinolic proton), 5H overlapping multiplets 2.0-2.4 (protons next to C=O), 3H triplet 1.22 (CH3 of ethyl), 9H singlet 1.17 (CH3 's to t-butyl) and 3H triplet 0.9 (terminal methyl); mass spectrum: m/e 424.

Workup

  1. customTo a Grignard solution, prepared from 5.05 g
  2. additionof copper iodide-tri-n-butylphosphine complex followed by dropwise addition of 49 g
  3. customUnreacted magnesium is removed by filtration
  4. washThe ethereal layer is washed successively with aqueous sodium thiosulfate solution, ammonium chloride solution, and water
  5. dry with materialdried over magnesium sulfate
  6. customto give an oil
  7. distillationDistillation at 0.05 mm
  8. custom(bath 100°-185° C.) gives 45.5 g
  9. additionof material containing unreacted

Sources & evidence

ORD record
ord-4f69b2d85a674d02b418708b3c04b3c0
Source dataset
uspto-grants-1978_08
Patent number
US04110368

Reaction notes

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