Hydrochloric Acid → cis 5,6-dihydro-6-(2-ethoxycarbonylethyl)-4-(4-methoxybenzylamino)-4H-thieno[2,3-b]thiopyran

HRID 2254311Notes

Reaction equation

HRID 2254311 reaction equation
O=[C:2]1[CH:7](CCC(OCC)=O)[CH2:6][S:5][C:4]2[S:15][CH:16]=[CH:17][C:3]1=2.[CH3:18][O:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24][NH2:25])=[CH:22][CH:21]=1.[BH4-].[Na+].Cl.[CH3:31][CH2:32][OH:33]>C1COCC1.C1(C)C=CC=CC=1.[Ti](Cl)(Cl)(Cl)Cl>[CH2:32]([O:33][C:20]([CH2:21][CH2:22][C@H:6]1[S:5][C:4]2[S:15][CH:16]=[CH:17][C:3]=2[C@@H:2]([NH:25][CH2:24][C:23]2[CH:26]=[CH:27][C:20]([O:19][CH3:18])=[CH:21][CH:22]=2)[CH2:7]1)=[O:19])[CH3:31]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 754524-MethoxybenzylamineHCID 4311764Sodium borohydrideHCID 678831665,6-Dihydro-4-oxo-5-(2-ethoxycarbonylethyl)thieno[2,3-b]thiopyran

Product 1

HCID 86747095cis 5,6-dihydro-6-(2-ethoxycarbonylethyl)-4-(4-methoxybenzylamino)-4H-thieno[2,3-b]thiopyran

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2 (10.4 g, 0.039 mol) in THF (110 ml) and toluene (110 ml) at 0° is added 4-methoxybenzylamine (25.5 ml, 26.8 g, 0.195 mol). Titanium tetrachloride (2.2 ml, 3.8 g, 0.02 mol) is added to the cold solution and the resulting mixture is stirred for 0.75-1 hour. The mixture is added to a cold (0°) stirred suspension of NaBH4 (4.5 g, 0.12 mol) in EtOH (900 ml). The resulting mixture is stirred for about 1 hour and acidified to pH 1 with 3N HCl. The solvent is removed in vacuo and the residue partitioned between EtOAc and saturated NaHCO3 solution. The EtOAc layer is separated, dried and concentrated to dryness to yield 3 wherein R1, R2, R3 and R4 are each H.

Workup

  1. additionThe mixture is added to a cold (0°)
  2. stirringstirred
  3. stirringThe resulting mixture is stirred for about 1 hour
  4. customThe solvent is removed in vacuo
  5. customthe residue partitioned between EtOAc and saturated NaHCO3 solution
  6. customThe EtOAc layer is separated
  7. customdried
  8. concentrationconcentrated to dryness
  9. customto yield 3 wherein R1, R2, R3 and R4

Sources & evidence

ORD record
ord-68e0aeaf7c0440b7bf7780fc3524c4be
Source dataset
uspto-grants-1993_08
Patent number
US05235059

Reaction notes

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