Carbon Dioxide → HCID 67168946, compound

HRID 1517553Notes

Reaction equation

HRID 1517553 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([CH2:6][CH2:7][OH:8])=[CH:2]1.C(OC([N:16]1[CH2:21][CH2:20][C:19](=O)[CH2:18][CH2:17]1)=O)(C)(C)C.[F:23][C:24]([F:29])([F:28])[C:25]([OH:27])=[O:26].C(=O)=O>ClCCl.C(OC)(C)(C)C>[F:23][C:24]([F:29])([F:28])[C:25]([O-:27])=[O:26].[S:1]1[C:2]2[C:19]3([CH2:20][CH2:21][NH2+:16][CH2:17][CH2:18]3)[O:8][CH2:7][CH2:6][C:3]=2[CH:4]=[CH:5]1

Participants

7

Reactant 4

HCID 280Carbon DioxideHCID 6422Trifluoroacetic acidHCID 83731Thiophene-3-ethanolHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 67168946HCID 67168946, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

3-Thiopheneethanol (123.03 mL, 1.11 mol) is added to a solution of N-tert-butoxycarbonyl-4-piperidone (185 g, 928.48 mmol) in dichloromethane (1300 mL) and stirred at room temperature. Then trifluoroacetic acid (280.82 mL, 3.71 moles) is added dropwise (5 min) while cooling with an ice/water bath (internal temperature=14° C.-30° C., caution: CO2 evolution). The reaction mixture is gradually warmed to ambient temperature and stirred at that temperature for 20 hr. The solvent is evaporated to provide a beige crystalline solid upon cooling in vacuo. The solid is slurried in methyl t-butyl ether (200 mL), filtered, washed with methyl t-butyl ether (2×1000 mL) and dried under vacuum to afford 4′,5′-dihydrospiro[piperidine-4,7′-thieno[2,3-c]pyran]-1-ium trifluoroacetate as a white solid in 95% yield. MS=(m/z): 210 (M+1). 10 M sodium hydroxide (220.36 mL, 2.20 mol) is added to a stirred suspension of 4′,5′-dihydrospiro[piperidine-4,7′-thieno[2,3-c]pyran]-1-ium trifluoroacetate (285 g, 881.44 mmol) in dichloromethane (1 L) with cooling (ice/water bath) and the resulting mixture is stirred till a biphasic mixture is obtained. The phases are separated and the aqueous layer is extracted with dichloromethane (2×200 mL). Combined organics are concentrated under vacuum to obtain a thick oil which is triturated with water to obtain a light yellow precipitate. The precipitate is filtered, washed with water (300 mL) and hexane (200 mL) and dried under vacuum at 35° C. for 20 hr. to yield the title compound as a light yellow solid in 86% yield. MS (m/z): 210 (M+1).

Workup

  1. temperatureThe reaction mixture is gradually warmed to ambient temperature
  2. stirringstirred at that temperature for 20 hr
  3. customThe solvent is evaporated
  4. customto provide a beige crystalline solid
  5. temperatureupon cooling in vacuo
  6. filtrationfiltered
  7. washwashed with methyl t-butyl ether (2×1000 mL)
  8. customdried under vacuum

Sources & evidence

ORD record
ord-c846e0eaf00e4a5faf9c808c2ed10c49
Source dataset
uspto-grants-2012_07
Patent number
US08232289B2

Reaction notes

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