1,1,3,3-Tetramethylguanidine → Methyl 2-(benzyloxycarbonylamino)-2-(1,4-dioxaspiro[4.5]decan-8-ylidene)acetate

HRID 388914Notes

Reaction equation

HRID 388914 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][C:8](=O)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[CH2:12]([O:19][C:20]([NH:22][CH:23](P(OC)(OC)=O)[C:24]([O:26][CH3:27])=[O:25])=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.CN(C)C(N(C)C)=N>CCOC(C)=O>[CH2:12]([O:19][C:20]([NH:22][C:23](=[C:8]1[CH2:9][CH2:10][C:5]2([O:4][CH2:3][CH2:2][O:1]2)[CH2:6][CH2:7]1)[C:24]([O:26][CH3:27])=[O:25])=[O:21])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 664601,1,3,3-TetramethylguanidineHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 2734718Methyl 2-{[(benzyloxy)carbonyl]amino}-2-(dimethyl phosphono)acetate

Product 1

HCID 11256965Methyl 2-(benzyloxycarbonylamino)-2-(1,4-dioxaspiro[4.5]decan-8-ylidene)acetateYield 26.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent3×

Procedure

A solution of 1,4-dioxaspiro[4.5]decan-8-one (15 g, 96 mmol) in EtOAc (150 mL) was added to a solution of methyl 2-(benzyloxycarbonylamino)-2-(dimethoxyphosphoryl)acetate (21.21 g, 64.0 mmol) in 1,1,3,3-tetramethylguanidine (10.45 mL, 83 mmol) and EtOAc (150 mL). The resulting solution was the stirred at ambient temperature for 72 h and then it was diluted with EtOAc (25 mL). The organic layer was washed with 1N HCl (75 mL), H2O (100 mL) and brine (100 mL), dried (MgSO4), filtered and concentrated. The residue was purified via BIOTAGE® (5% to 25% EtOAc/Hexanes; 300 g column). The combined fractions containing the product were then concentrated under vacuum and the residue was re-crystallized from hexanes/EtOAc to give white crystals that corresponded to methyl 2-(benzyloxycarbonylamino)-2-(1,4-dioxaspiro[4.5]decan-8-ylidene)acetate (6.2 g) 1H NMR (400 MHz, CDCl3-d) δ ppm 7.30-7.44 (5H, m), 6.02 (1H, br. s.), 5.15 (2H, s), 3.97 (4H, s), 3.76 (3H, br. s.), 2.84-2.92 (2H, m), 2.47 (2H, t, J=6.40 Hz), 1.74-1.83 (4H, m). LC (Cond. OL1): Rt=2.89 min. LC-MS: Anal. Calcd. for [M+Na]+ C19H23NNaO6: 745.21. found: 745.47.

Workup

  1. washThe organic layer was washed with 1N HCl (75 mL), H2O (100 mL) and brine (100 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified via BIOTAGE® (5% to 25% EtOAc/Hexanes; 300 g column)
  6. additionThe combined fractions containing the product
  7. concentrationwere then concentrated under vacuum
  8. customthe residue was re-crystallized from hexanes/EtOAc

Sources & evidence

ORD record
ord-53f8950a7d664d0daa3da5d2e9912f9f
Source dataset
uspto-grants-2013_02
Patent number
US08377980B2

Reaction notes

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