Phosphorus oxide (P4O10) → 6,7-difluoro-3,4-dihydroisoquinolin-1(2H)-one

HRID 1843955Notes

Reaction equation

HRID 1843955 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][C:15]=1[F:16])[CH2:5][CH2:6][NH:7][C:8](=O)[O:9]CC.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>O=P(Cl)(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][C:15]=1[F:16])[C:8](=[O:9])[NH:7][CH2:6][CH2:5]2

Participants

4

Reactant 2

HCID 14812Phosphorus oxide (P4O10)HCID 89964322Ethyl 3,4-difluorophenethylcarbamate

Product 1

HCID 899639446,7-difluoro-3,4-dihydroisoquinolin-1(2H)-oneYield 20%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

Using an analogous reaction procedure and workup as described in example 1 for the preparation of intermediate I-1d above, ethyl 3,4-difluorophenethylcarbamate (I-49c: 5 g, 21.8340 mmol) in POCl3 (43.6 mL) was reacted with P2O5 (6.19 g, 43.6681 mmol) at 110° C. for 2 hours to afford the crude product. Purification by column chromatography on silica gel (50% ethyl acetate in hexane) afforded 800 mg of the product (18.91% yield).

Workup

  1. customan analogous reaction procedure
  2. customworkup as described in example 1 for the preparation of intermediate I-1d above
  3. customto afford the crude product
  4. customPurification by column chromatography on silica gel (50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-ced4bd7d96a64c07ae2bdcabbc028fec
Source dataset
uspto-grants-2015_02
Patent number
US08946260B2

Reaction notes

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