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

HRID 1745414Notes

Reaction equation

HRID 1745414 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 hours 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 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 sillicagel (90 g) using a mixture of dichloromethane/ethanol/25% ammonia in water 100:10:0.7 as eluent. 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 extracted with dichloromethane (3×)
  5. dry with materialThe combined organic phases were dried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent removed in vacuo
  8. customThe residue was purified by flash chromatography on sillicagel (90 g)
  9. additiona mixture of dichloromethane/ethanol/25% ammonia in water 100:10:0.7 as eluent
  10. customPure fractions were collected
  11. customthe solvent evaporated in vacuo

Sources & evidence

ORD record
ord-7b707a86624e4ce186af189ad5ed05ec
Source dataset
uspto-grants-2006_03
Patent number
US07019026B1

Reaction notes

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