Diisopropylethylamine → 3-{2-[8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl]ethyl}-3-oxido-7-oxo-8-propyl-2,4,6-trioxa-3-phosphaundec-1-yl 2-propylpentanoate

HRID 852469Notes

Reaction equation

HRID 852469 reaction equation
[O:1]=[C:2]1[C:10](=[O:11])[C:9]2[N:8]([CH2:12][CH2:13][P:14](=[O:17])([OH:16])[OH:15])[CH2:7][CH2:6][CH2:5][NH:4][C:3]1=2.C(N(CC)[CH:22]([CH3:24])[CH3:23])(C)C.Cl[CH2:28][O:29][C:30](=[O:38])[CH:31]([CH2:35][CH2:36][CH3:37])[CH2:32][CH2:33][CH3:34]>CN(C=O)C>[CH2:32]([CH:31]([CH2:24][CH2:22][CH3:23])[C:30]([O:29][CH2:28][O:17][P:14]([CH2:13][CH2:12][N:8]1[CH2:7][CH2:6][CH2:5][NH:4][C:3]2[C:2](=[O:1])[C:10](=[O:11])[C:9]1=2)(=[O:15])[O:16][CH2:28][O:29][C:30](=[O:38])[CH:31]([CH2:35][CH2:36][CH3:37])[CH2:32][CH2:33][CH3:34])=[O:38])[CH2:33][CH3:34]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 6918236PerzinfotelHCID 128400662-Propyl-pentanoic acid chloromethyl ester

Product 1

HCID 112384913-{2-[8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl]ethyl}-3-oxido-7-oxo-8-propyl-2,4,6-trioxa-3-phosphaundec-1-yl 2-propylpentanoateYield 56.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A solution of the starting [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)ethyl]phosphonic acid (26 mmol, 6.765 g) in dry DMF (250 mL) was treated with N,N-diisopropylethylamine (104 mmol, 13.442 g) followed by 2-propyl-pentanoic acid chloromethyl ester (88 mmol, 17 g, synthesis described below) at ambient temperature and under exclusion of moisture. The reaction mixture was heated to 65° C. and held, with stirring, at 65° C. for over 16 hours. The solvent was removed by vacuum distillation and the residue was partitioned (2×) between water and ether. The organic phase was separated, dried over magnesium sulfate, filtered, and evaporated to dryness affording about 16 g of crude product as a dense yellow oil. This oil was flash chromatographed on 350 g silica gel. Elution with 8% methanol/ethyl acetate afforded 8.4 g (56%) of the desired product as a colorless solidified wax. MS (ES+): m/e 573 (M+H).

Workup

  1. customThe solvent was removed by vacuum distillation
  2. customthe residue was partitioned (2×) between water and ether
  3. customThe organic phase was separated
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customaffording about 16 g of crude product as a dense yellow oil
  8. customchromatographed on 350 g silica gel
  9. washElution with 8% methanol/ethyl acetate

Sources & evidence

ORD record
ord-b61b263d3b6f49a48f1d1b9532d39e54
Source dataset
uspto-grants-2007_08
Patent number
US07253153B2

Reaction notes

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