Acetic Acid → 8-Fluorenylmethoxycarbonylaminooctanoic acid

HRID 1419688Notes

Reaction equation

HRID 1419688 reaction equation
[C:1]1([CH2:14][O:15][C:16](Cl)=[O:17])[C:13]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[NH2:19][CH:20]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]C)C(O)=O.[C:30]([OH:33])(=[O:32])[CH3:31]>C([O-])([O-])=O.[Na+].[Na+].O1CCOCC1>[C:1]1([CH2:14][O:15][C:16]([NH:19][CH2:20][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:31][C:30]([OH:33])=[O:32])=[O:17])[C:13]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 695222-Aminooctanoic acidHCID 14261773Fluorenylmethyl chloroformate

Product 1

HCID 542906718-Fluorenylmethoxycarbonylaminooctanoic acid

Reagents, catalysts & solvents 2

HCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

Fluorenylmethoxycarbonyl chloride (4.87 g, 0.02 mol) to a mixture of aminooctanoic acid (3.0 g ,0.02 mol) in 200 mL of 10% Na2CO3 (aq) and dioxane (150 mL) at 0° C. The mixture was stirred for 2.5 h at 0° C., acidified to pH 5 with acetic acid and extracted three times with CHCl3. The combined organic extracts were washed with H2O, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, CHCl3 →95:5 CHCl3 --MeOH) to afford 8-fluorenylmethoxycarbonylaminooctanoic acid (6.4 g) as a solid: MS 382 (MH+). The product was dissolved in CH2Cl2 (40 mL), cooled to 0° C., and treated with methoxymethyl amine hydrochloride (2.05 g, 21.1 mimol), triethylamine (8.1 mL) and BOP reagent (8.0 g). This mixture was stirred for 12 h at 0° C., washed sequentially with 3N HCI, NaHCO3 (sat"d. aq.) and brine. The organic phase was dried (Na2SO4) and concentrated. in vacuo. The residue was purified by flash column chromatography (silica gel; CHCl3 →98:2 CHCl3 --MeOH) to afford 8-fluorenylmethoxycarbonyl-aminooctanoic acid N,N-methoxymethyl amide (7.1 g): MS m/z 425 (MH+). A solution of the product (6.8 g) in THF (80 mL) was cooled to -40° C. and treated dropwise with 1.0M DIBAL/THF (48.5 mL). The mixture was stirred an additional 15 min, quenched with 3N HCI (50 mL) and warmed to room temperature. The resulting aqueous layer was extracted repeatedly with CHCl3 and the combined organic extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by chromatography (silica gel; CH2Cl2 →2% MeOH--CH2Cl2) to afford aldehyde 13a as a solid: 5.2 g; MS m/z 366 (MH+).

Workup

  1. extractionextracted three times with CHCl3
  2. washThe combined organic extracts were washed with H2O
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography (silica gel, CHCl3 →95:5 CHCl3 --MeOH)

Sources & evidence

ORD record
ord-9959d6e75438469bb6bfaf49aea2a09a
Source dataset
uspto-grants-1999_03
Patent number
US05888971

Reaction notes

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