Phosphorus oxychloride → tert-Butyl 4-chloro-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate

HRID 1713112Notes

Reaction equation

HRID 1713112 reaction equation
O[C:2]1[C:12]2[CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8][CH2:7][C:6]=2[N:5]=[CH:4][N:3]=1.O=P(Cl)(Cl)[Cl:22]>C1(C)C=CC=CC=1>[Cl:22][C:2]1[C:12]2[CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8][CH2:7][C:6]=2[N:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178451657HCID 178451657, compound

Product 1

HCID 39345748tert-Butyl 4-chloro-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of tert-butyl 4-hydroxy-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate (4.3 g, 16.2 mmol) and POCl3 (2.3 ml) in toluene (30 mL) is heated at 90° C. for 1 hr. The solvent is removed in vacuo and EtOAc (30 ml) and water (30 ml) are added to the residue. NaHCO3 is carefully added until the pH of the aqueous layer is greater than 7. The layers are separated and the aqueous layer is extracted with EtOAc (2×30 ml). The combined extracts are washed with brine (50 ml) and dried (Na2SO4), and the solvent is evaporated. Flash column purification of the residue with EtOAc/hexane (6:1) provides the title compound as a light yellow solid.

Workup

  1. customThe solvent is removed in vacuo and EtOAc (30 ml) and water (30 ml)
  2. additionare added to the residue
  3. additionNaHCO3 is carefully added until the pH of the aqueous layer
  4. customThe layers are separated
  5. extractionthe aqueous layer is extracted with EtOAc (2×30 ml)
  6. washThe combined extracts are washed with brine (50 ml)
  7. dry with materialdried (Na2SO4)
  8. customthe solvent is evaporated
  9. customFlash column purification of the residue with EtOAc/hexane (6:1)

Sources & evidence

ORD record
ord-8d37c9994e7b46c4ab4fd4d9100aab53
Source dataset
uspto-grants-2010_09
Patent number
US07795262B2

Reaction notes

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