Potassium Carbonate → ethyl 9-bromo-8-fluoro-5,6-dihydro-4H-4,6-methanobenzo[3,4]cyclohepta[1,2-b]thiophene-2-carboxylate

HRID 575451Notes

Reaction equation

HRID 575451 reaction equation
[Br:1][C:2]1[C:3]([F:17])=[CH:4][C:5]2[CH:11]3[CH2:12][CH:9]([CH2:10]3)[C:8](Cl)=[C:7]([CH:14]=O)[C:6]=2[CH:16]=1.[SH:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Br:1][C:2]1[C:3]([F:17])=[CH:4][C:5]2[CH:11]3[CH2:10][CH:9]([CH2:12]3)[C:8]3[S:18][C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:14][C:7]=3[C:6]=2[CH:16]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 12185Ethyl ThioglycolateHCID 86693512HCID 86693512, compound

Product 1

HCID 86693514ethyl 9-bromo-8-fluoro-5,6-dihydro-4H-4,6-methanobenzo[3,4]cyclohepta[1,2-b]thiophene-2-carboxylateYield 27%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

Into a pressure tube containing a solution of 2-bromo-8-chloro-3-fluoro-6,7-dihydro-5H-5,7-methanobenzo[7]annulene-9-carbaldehyde (125 mg at 79% purity LCMS-UV215) in anhydrous N,N-dimethylformamide (0.5 mL) was introduced ethyl mercaptoacetate (46 mg, 0.38 mmol as a solution in 0.5 mL of anhydrous N,N-dimethylformamide) and finely powdered potassium carbonate (53 mg, 0.38 mmol). After warming to 60° C. for 4 hr, the reaction mixture was concentrated in vacuo, the residue suspended in ethyl acetate (15 mL) and washed with water (2×10 ml) and brine (10 ml). The organic extract was dried over sodium sulfate, filtered and the filtrate adsorbed onto silica gel in vacuo. Purification of the dry-loaded material by silica gel flash column chromatography (eluent: heptane/ethyl acetate gradient) furnished the title compound (39 mg, 0.10 mmol, 27% over 2 steps) as a colorless solid: 1H NMR (500 MHz, CDCl3) δ 1.40 (t, J=7.09 Hz, 3H), 1.71 (d, J=8.83 Hz, 2H), 2.86-2.95 (m, 2H), 3.57 (m, 2H), 4.37 (q, J=7.04 Hz, 2H), 6.91 (dd, J=9.14, 2.21 Hz, 1H), 8.06 (dd, J=6.94, 2.21 Hz, 1H), 8.22 (d, J=1.89 Hz, 1H); M+1=381/383.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. washwashed with water (2×10 ml) and brine (10 ml)
  3. extractionThe organic extract
  4. dry with materialwas dried over sodium sulfate
  5. filtrationfiltered
  6. customPurification of the dry-loaded material by silica gel flash column chromatography (eluent: heptane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-7a86310f59884f868b208b8f49bbf586
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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