1,1,3,3-Tetramethylguanidine → Methyl (2Z)-2-{[(benzyloxy)carbonyl]amino}-3-(1-methylcyclohexyl)acrylate

HRID 2220815Notes

Reaction equation

[CH3:1][C:2]1([CH:8]=O)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[CH2:10]([O:17][C:18]([NH:20][CH:21](P(OC)(OC)=O)[C:22]([O:24][CH3:25])=[O:23])=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CN(C)C(N(C)C)=N>O1CCCC1>[CH2:10]([O:17][C:18]([NH:20]/[C:21](=[CH:1]\[C:2]1([CH3:8])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1)/[C:22]([O:24][CH3:25])=[O:23])=[O:19])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

Conditions

Temperature: -78 °C

Procedure

1-Methylcyclohexanecarbaldehyde (2.66 g, 21.08 mmol) and methyl {[(benzyloxy)carbonyl]amino}(dimethoxyphosphoryl)acetate (6.63 g, 20.02 mmol, 0.95 equivalent) are dissolved in 75 ml of tetrahydrofuran and cooled to −78° C. At −78° C., N,N,N′,N′-tetramethylguanidine (27.92 g, 0.24 mol, 11.5 equivalents) is added dropwise and then stirred at −78° C. for 15 min and subsequently at room temperature for 4 days. The mixture is then extracted by shaking with ethyl acetate (twice 100 ml) and water, and the combined organic phases are washed with saturated sodium chloride solution and dried over sodium sulphate. After concentration, the crude product is chromatographed (Biotage 40M, cyclohexane/ethyl acetate 6/1, 27.5 ml/min). 0.91 g (13% of theory) of the title compound is obtained.

Workup

extractionThe mixture is then extracted
stirringby shaking with ethyl acetate (twice 100 ml) and water
washthe combined organic phases are washed with saturated sodium chloride solution
dry with materialdried over sodium sulphate
concentrationAfter concentration
customthe crude product is chromatographed (Biotage 40M, cyclohexane/ethyl acetate 6/1, 27.5 ml/min)

Sources & evidence

ORD record: ord-66be9f11b08e421b8c43c76e0407ba97
Source dataset: uspto-grants-2008_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07368424B2

Reaction notes

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