Phosphate → 2-amino-7-aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester

HRID 1242070Notes

Reaction equation

HRID 1242070 reaction equation
[C:1]([O:5][C:6]([C:8]1[C:16]2[CH2:15][CH2:14][O:13][CH:12]([CH2:17][NH:18]C(OCC(Cl)(Cl)Cl)=O)[C:11]=2[S:10][C:9]=1[NH2:27])=[O:7])([CH3:4])([CH3:3])[CH3:2].P([O-])([O-])([O-])=O>O1CCCC1.[Zn]>[C:1]([O:5][C:6]([C:8]1[C:16]2[CH2:15][CH2:14][O:13][CH:12]([CH2:17][NH2:18])[C:11]=2[S:10][C:9]=1[NH2:27])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 1061PhosphateHCID 695856802-amino-7-((2,2,2-trichloro-ethoxycarbonylamino)methyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester

Product 1

HCID 695860292-amino-7-aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl esterYield 66.8%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Procedure

The above 2-amino-7-((2,2,2-trichloro-ethoxycarbonylamino)methyl)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester (4.0 g, 8.0 mmol) was dissolved in a mixture of tetrahydrofuran (15 ml) and a aqueous phosphate buffer (pH 3; 5 ml) followed by addition of zinc (16 g, 0.244 mol). The reaction mixture was stirred for 6 h at room temperature at which time the solvent was removed in vacuo. To the residue was added diethyl ether (20 ml) and water (40 ml). Sodium carbonate was added to the aqueous phase until pH=8 and the aqueous phase was extracted with dichloromethane (3×). The combined organic phases were, dried (MgSO4), filtered and the solvent removed in vacuo. The residue was purified by flash chromatography on silica gel (90 g) using a mixture of dichloromethane/ethanol/25% ammonia in water 100:10:0.7 as eluant. Pure fractions were collected and the solvent evaporated in vacuo affording 1.52 g (61%) of 2-amino-7-aminomethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid tert-butyl ester.

Workup

  1. customwas removed in vacuo
  2. additionTo the residue was added diethyl ether (20 ml) and water (40 ml)
  3. additionSodium carbonate was added to the aqueous phase until pH=8
  4. extractionthe aqueous phase was extracted with dichloromethane (3×)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent removed in vacuo
  8. customThe residue was purified by flash chromatography on silica gel (90 g)
  9. additiona mixture of dichloromethane/ethanol/25% ammonia in water 100:10:0.7 as eluant
  10. customPure fractions were collected
  11. customthe solvent evaporated in vacuo

Sources & evidence

ORD record
ord-b1f66677ca794cd2948ae2d8f35e16b2
Source dataset
uspto-grants-2006_10
Patent number
US07115624B1

Reaction notes

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