Pyridine → 1-Chloro-2,2-difluoro-1-phenyl-1,3,6,7,9,10-hexahydro-2H-8-aza-cyclohepta[e]indene-8-carboxylic acid ethyl ester

HRID 925206Notes

Reaction equation

HRID 925206 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:28][CH2:27][C:10]2[C:11]3[C:12](O)([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:13]([F:19])([F:18])[CH2:14][C:15]=3[CH:16]=[CH:17][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2].N1C=CC=CC=1.S(Cl)([Cl:37])=O>>[CH2:1]([O:3][C:4]([N:6]1[CH2:28][CH2:27][C:10]2[C:11]3[C:12]([Cl:37])([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:13]([F:19])([F:18])[CH2:14][C:15]=3[CH:16]=[CH:17][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

4

Reactant 3

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 867253182,2-Difluoro-1-hydroxy-1-phenyl-1,3,6,7,9,10-hexahydro-2H-8-aza-cyclohepta[e]indene-8-carboxylic acid ethyl ester

Product 1

HCID 867253171-Chloro-2,2-difluoro-1-phenyl-1,3,6,7,9,10-hexahydro-2H-8-aza-cyclohepta[e]indene-8-carboxylic acid ethyl ester

Conditions

Temperature
70 °C

Procedure

Into a 100 ml flask, the product from step (c) (5.78 g, 14.93 mmol) dissolved in thionyl chloride (50 ml) was added. Pyridine (120 μL, 1.49 mmol) was added and the reaction mixture heated to 70° C. for 1 hour. The reaction mixture was allowed to cool to room temperature and the volatiles were evaporated in vacuo. The residue was partitioned between saturated aqueous Na2CO3 and EtOAc. The aqueous layer was extracted with EtOAc (3×). The combined EtOAc extracts were washed with brine, dried over Na2SO4, and solvent evaporated in vacuo to give the sub-title compound as an orange semi-solid (5.9 g) that was used directly in the next step. MS: ESI (positive): 405 (M+1).

Workup

  1. additionwas added
  2. temperatureto cool to room temperature
  3. customthe volatiles were evaporated in vacuo
  4. customThe residue was partitioned between saturated aqueous Na2CO3 and EtOAc
  5. extractionThe aqueous layer was extracted with EtOAc (3×)
  6. washThe combined EtOAc extracts were washed with brine
  7. dry with materialdried over Na2SO4, and solvent
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-60958ba46f4341509d3070b71bccb49a
Source dataset
uspto-grants-2016_03
Patent number
US09284277B2

Reaction notes

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