Hydrochloric Acid → 3-Chloro-1-(5,5-dimethyl-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)propan-1-one

HRID 1024056Notes

Reaction equation

HRID 1024056 reaction equation
[CH3:1][C:2]1([CH3:13])[CH2:12][C:5]2[S:6][C:7]([C:9]([OH:11])=O)=[CH:8][C:4]=2[CH2:3]1.[CH:14]([Mg]Br)=[CH2:15].[ClH:18].CCOCC>C1COCC1>[Cl:18][CH2:14][CH2:15][C:9]([C:7]1[S:6][C:5]2[CH2:12][C:2]([CH3:1])([CH3:13])[CH2:3][C:4]=2[CH:8]=1)=[O:11]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 580439285,5-dimethyl-4H,5H,6H-cyclopenta[b]thiophene-2-carboxylic acidHCID 178418507HCID 178418507, compound

Product 1

HCID 580442953-Chloro-1-(5,5-dimethyl-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)propan-1-oneYield 118%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with 113d (2.41 g, 10.0 mmol) and anhydrous THF (20 mL). The solution was cooled to −70° C., and 1 M vinylmagnesium bromide in THF (11 mL, 11.0 mmol) was added with the reaction temperature maintained below −60° C. The reaction mixture was stirred at −13 to −7° C. for 2 h and then warmed to room temperature over 30 min. The reaction was again cooled to −70° C., and a 2 M solution of hydrogen chloride in ether (22.5 ml, 45 mmol) was added. The reaction was then stored in a freezer at −10° C. overnight. After this time the mixture was evaporated under reduced pressure on a rotary evaporator, and the resulting residue partitioned between water (100 mL) and ether (100 mL). The ether extract was dried over sodium sulfate and evaporated under reduced pressure on a rotary evaporator to afford crude 113e (2.86 g, 118%) as a brown oil with approximately 75% purity (by NMR): 1H NMR (300 MHz, CDCl3) δ 7.45 (s, 1H), 3.89 (t, 2H, J=6.9 Hz), 3.30 (t, 2H, J=6.9 Hz), 2.75 (s, 2H), 2.59 (s, 2H), 1.24 (s, 6H)

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. customwas purged with nitrogen
  3. temperaturemaintained below −60° C
  4. temperaturewarmed to room temperature over 30 min
  5. temperatureThe reaction was again cooled to −70° C.
  6. waitThe reaction was then stored in a freezer at −10° C. overnight
  7. customAfter this time the mixture was evaporated under reduced pressure on a rotary evaporator
  8. customthe resulting residue partitioned between water (100 mL) and ether (100 mL)
  9. extractionThe ether extract
  10. dry with materialwas dried over sodium sulfate
  11. customevaporated under reduced pressure on a rotary evaporator

Sources & evidence

ORD record
ord-cc64319c243749e0a53edf3339469bd6
Source dataset
uspto-grants-2014_05
Patent number
US08722676B2

Reaction notes

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