Trimethyl phosphonoacetate → Methyl 2-[3-[[(1,1-dimethylethoxy)carbonyl]amino]cyclobutylidene]acetate

HRID 865704Notes

Reaction equation

HRID 865704 reaction equation
[CH3:1][O:2][C:3]([CH2:5]P(OC)(OC)=O)=[O:4].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[C:22]([O:26][C:27]([NH:29][CH:30]1[CH2:33][C:32](=O)[CH2:31]1)=[O:28])([CH3:25])([CH3:24])[CH3:23]>O1CCCC1>[C:22]([O:26][C:27]([NH:29][CH:30]1[CH2:33][C:32](=[CH:5][C:3]([O:2][CH3:1])=[O:4])[CH2:31]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

5

Reactant 3

HCID 80029Trimethyl phosphonoacetateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 23374584tert-Butyl 3-oxocyclobutylcarbamate

Product 1

HCID 23374583Methyl 2-[3-[[(1,1-dimethylethoxy)carbonyl]amino]cyclobutylidene]acetateYield 97.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

To a cooled (-70° C.) and stirred solution of trimethyl phosphonoacetate (1.5 g) in anhydrous tetrahydrofuran (40 ml) was added potassium bis(trimethylsilyl)amide (0.5M in toluene; 15.07 ml) at such a rate as to maintain the internal temperature below -62° C. (ca 8 min). After 15 minutes of stirring at -70° C., a solution of 3-(tert-butyloxycarbonylamino)cyclobutan-1-one (1.27 g) in anhydrous tetrahydrofuran (10 ml) was added over 9 minutes, under a nitrogen atmosphere. The mixture was then allowed to warm to room temperature and it was stirred for 1 hour before it was quenched with saturated aqueous ammonium chloride (40 ml). Products were extracted with ethyl acetate (2×50 ml) and the combined organic solutions were washed with brine (1×40 ml), dried (MgSO4) and concentrated. Flash chromatography of the residue (silica gel, hexane-ethyl acetate, 75:25) gave 1.61 g (97%) the title compound as a white solid; mp 79°-82° C. δ (250 MHz, CDCl3) 5.70 (1H, m, --CH--), 4.81 (1H, br s, --NH--), 4.32-4.13 (1H, m, --CH--), 3.69 (3H, s, --OMe), 3.64-3.50 (1H, m, --CH2 --), 3.26-3.10 (1H, m, --CH2 --), 3.00-2.86 (1H, m, --CH2 --), 2.80-2.68 (1H, m, --CH2 --), 1.45 (9H, s, t--Bu); m/z (CI) 240 (M- -1). (Found: C, 60.28; H, 7.87; N, 5.76. C12H19NO4 ×0.03 C6H14 requires: C, 59.99; H, 8.02; N, 5.75%.)

Workup

  1. temperatureto maintain the internal temperature below -62° C. (ca 8 min)
  2. temperatureto warm to room temperature
  3. stirringit was stirred for 1 hour before it
  4. customwas quenched with saturated aqueous ammonium chloride (40 ml)
  5. extractionProducts were extracted with ethyl acetate (2×50 ml)
  6. washthe combined organic solutions were washed with brine (1×40 ml)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-8509721a38104bb48d6ca91f77c95f64
Source dataset
uspto-grants-1996_10
Patent number
US05567726

Reaction notes

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