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

HRID 1694432Notes

Reaction equation

HRID 1694432 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) was treated with 1,4-cyclohexanedione monoethylene ketal (11.3 mg, 72.0 mmol), followed by dibutyltin dichloride (1.098 gr, 3.6 mmol). After 5 min, phenyl silane (9.74 ml, 79.2 mmol) was added and the reaction mixture was stirred overnight at room temperature. After concentration, the residue was dissolved in EtOAc washed with NaHCO3 then brine. The organic layer was separated, dried on Na2SO4, filtered and concentrated. The crude material was diluted in hexane (500 ml). After filtration, the mother liquor was 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). 1H NMR (CDCl3, 400 MHz): 6.90 (br s, 1H), 6.65 (s, 1H), 3.95 (s, 4H), 3.78 (s, 3H), 3.35 (m, 1H), 2.00 (m, 2H), 1.80 (m, 2H), 1.65 (m, 4H).

Workup

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

Sources & evidence

ORD record
ord-fb17a52522c743a9870829f9069012cb
Source dataset
uspto-grants-2012_04
Patent number
US08158675B2

Reaction notes

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