3-Methyl-2-thiophenecarboxaldehyde → HCID 131726680, compound

HRID 2267647Notes

Reaction equation

HRID 2267647 reaction equation
[CH3:1][O:2][C:3]([CH:5](P(OC)(OC)=O)[NH:6][C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8])=[O:4].[CH3:23][C:24]1[CH:28]=[CH:27][S:26][C:25]=1[CH:29]=O.C1CCN2C(=NCCC2)CC1>ClCCl>[CH2:10]([O:9][C:7]([NH:6]/[C:5](=[CH:29]\[C:25]1[S:26][CH:27]=[CH:28][C:24]=1[CH3:23])/[C:3]([O:2][CH3:1])=[O:4])=[O:8])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 799113-Methyl-2-thiophenecarboxaldehydeHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2734718Methyl 2-{[(benzyloxy)carbonyl]amino}-2-(dimethyl phosphono)acetate

Product 1

HCID 131726680HCID 131726680, compoundYield 81.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A stirred solution of N-(benzyloxycarbonyl)-α-phosphonoglycine trimethyl ester (5.01 g, 15.1 mmol) and 3-methylthiophene-2-carbaldehyde (7.5:1 mixture with 4-methylthiophene-2-carbaldehyde, 2.48 g, 19.6 mmol) in dry dichloromethane (100 mL), was cooled to 0° C. and treated dropwise with DBU (2.76 g, 18.1 mmol). The mixture was warmed to ambient temperature and stirred overnight. The solution was concentrated, taken up in ethyl acetate (150 mL) and washed with 5% hydrochloric acid (2×75 mL). The organic extract was washed with saturated aqueous sodium bicarbonate (2×75 mL), water (75 mL), dried (magnesium sulfate), filtered and evaporated. The residue was purified by flash chromatography (20-40% ethyl acetate/hexanes gradient) to afford the title compound (4.07 g, 81%) as an orange oil. The product is a mixture of 3- and 4-methylthiophene isomers (6.8:1). 1H NMR major isomer: (300 MHz, d6-DMSO) δ2.33 (s, 3H), 3.72, (s, 3H), 5.13 (bs, 2H), 7.01 (d, 1H, J=5.3 Hz), 7.18-7.52 (m, 5H), 7.60-7.85 (m, 2H), 8.83 (s, 1H). MS APCI, m/z=354(M+Na). LC/MS: 2.43 min.

Workup

  1. concentrationThe solution was concentrated
  2. washwashed with 5% hydrochloric acid (2×75 mL)
  3. extractionThe organic extract
  4. washwas washed with saturated aqueous sodium bicarbonate (2×75 mL), water (75 mL)
  5. dry with materialdried (magnesium sulfate)
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by flash chromatography (20-40% ethyl acetate/hexanes gradient)

Sources & evidence

ORD record
ord-3db75608b9a54c3a828142255d92c433
Source dataset
uspto-grants-2010_12
Patent number
US07858776B2

Reaction notes

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