Phosphorus oxychloride → 4-chloro-5,8-dihydro-6H-spiro[1-benzothieno[2,3-d]pyrimidine-7,2'-[1,3]dioxolane]

HRID 1292970Notes

Reaction equation

HRID 1292970 reaction equation
O=P(Cl)(Cl)[Cl:3].[O:6]1[CH2:10][CH2:9][O:8][C:7]21[CH2:15][CH2:14][C:13]1[C:16]3[C:21](=O)[NH:20][CH:19]=[N:18][C:17]=3[S:23][C:12]=1[CH2:11]2>C(N(CC)CC)C>[Cl:3][C:21]1[C:16]2[C:13]3[CH2:14][CH2:15][C:7]4([CH2:11][C:12]=3[S:23][C:17]=2[N:18]=[CH:19][N:20]=1)[O:8][CH2:9][CH2:10][O:6]4

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 17990151HCID 17990151, compound

Product 1

HCID 179901054-chloro-5,8-dihydro-6H-spiro[1-benzothieno[2,3-d]pyrimidine-7,2'-[1,3]dioxolane]Yield 97%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a stirring 0° C. POCl3 (200 mL) solution of 3,5,6,8-tetrahydro-4H-spiro[1-benzothieno[2,3-d]pyrimidine-7,2′-[1,3]dioxolan]-4-one (20.0 g, 0.076 mol) was added triethylamine (200 mL) from a dropping funnel over a 15 min. period. The contents were allowed to warm to rt, and then heated to 80° C. After 3 h, the contents were removed from heating, and allowed to cool to rt. The heterogeneous mixture was concentrated under reduced pressure, the residue diluted with ethyl acetate (100 mL), and again concentrated. The residue was diluted with ethyl acetate (100 mL) and the heterogeneous mixture poured onto a stirring mixture of ice-water/sq. NaHCO3 (800 mL). After 5 min. stirring, the now pH=7 contents were filtered and the solid filter cake washed with water. The product was dried in vacuum oven overnight to afford the desired product (20.7 g, 97%) as an off-white solid. 1H-NMR (DMSO-d6) δ 8.82 (s, 1H), 3.97 (s, 4H), 3.10 (t, 2H), 3.07 (s, 2H), 1.95 (t, 2H); LCMS RT=2.45 min; [M+H]+=283.1.

Workup

  1. customTo a stirring 0° C
  2. temperatureheated to 80° C
  3. customthe contents were removed
  4. temperaturefrom heating
  5. temperatureto cool to rt
  6. concentrationThe heterogeneous mixture was concentrated under reduced pressure
  7. additionthe residue diluted with ethyl acetate (100 mL)
  8. concentrationagain concentrated
  9. additionThe residue was diluted with ethyl acetate (100 mL)
  10. additionthe heterogeneous mixture poured onto a stirring mixture of ice-water/sq
  11. filtrationthe now pH=7 contents were filtered
  12. filtrationthe solid filter cake
  13. washwashed with water
  14. customThe product was dried in vacuum oven overnight

Sources & evidence

ORD record
ord-1ae7c17eb0e64ba6a003572b7f753df8
Source dataset
uspto-grants-2007_07
Patent number
US07238701B2

Reaction notes

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