Phenylsilane → 5-Bromo-3-(1,4-dioxa-spiro[4.5]dec-8-ylamino)-thiophene-2-carboxylic acid methyl ester

HRID 244889Notes

Reaction equation

HRID 244889 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([Br:11])=[CH:8][C:9]=1[NH2:10])=[O:4].[CH2:12]1[O:22][C:15]2([CH2:20][CH2:19][C:18](=O)[CH2:17][CH2:16]2)[O:14][CH2:13]1.C1([SiH3])C=CC=CC=1>C1COCC1.C([Sn](Cl)(Cl)CCCC)CCC>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([Br:11])=[CH:8][C:9]=1[NH:10][CH:18]1[CH2:19][CH2:20][C:15]2([O:22][CH2:12][CH2:13][O:14]2)[CH2:16][CH2:17]1)=[O:4]

Participants

6

Reactant 3

HCID 12752PhenylsilaneHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 20158931Methyl 3-amino-5-bromothiophene-2-carboxylate

Product 1

HCID 597523595-Bromo-3-(1,4-dioxa-spiro[4.5]dec-8-ylamino)-thiophene-2-carboxylic acid methyl esterYield 92%

Reagents, catalysts & solvents 2

HCID 12688Dibutyltin dichlorideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 3-amino-5-bromo-thiophene-2-carboxylic acid methyl ester (17.0 g, 72.0 mmol) in dry THF (21 mL) is treated with 1,4-cyclohexanedione monoethylene ketal (11.3 mg, 72.0 mmol), followed by dibutyltin dichloride (1.098 g, 3.6 mmol). After 5 min, phenyl silane (9.74 mL, 79.2 mmol) is added and the reaction mixture is stirred over-night at room temperature. After concentration, the residue is dissolved in EtOAc washed with NaHCO3 then brine. The organic layer is separated, dried on Na2SO4, filtered and concentrated. The crude material is diluted in hexane (500 mL). After filtration, the mother liquor is evaporated to dryness to give 5-bromo-3-(1,4-dioxa-spiro[4.5]dec-8-ylamino)-thiophene-2-carboxylic acid methyl ester (24.79 g, 92% yield).

Workup

  1. concentrationAfter concentration
  2. dissolutionthe residue is dissolved in EtOAc
  3. washwashed with NaHCO3
  4. customThe organic layer is separated
  5. customdried on Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. additionThe crude material is diluted in hexane (500 mL)
  9. filtrationAfter filtration
  10. customthe mother liquor is evaporated to dryness

Sources & evidence

ORD record
ord-a7bbb955ee40446780fe6268ab0a8678
Source dataset
uspto-grants-2014_02
Patent number
US08658674B2

Reaction notes

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