Triethylamine → HCID 9954840, compound

HRID 1872750Notes

Reaction equation

HRID 1872750 reaction equation
[CH2:1]([C@H:8]([NH2:23])[CH2:9][N:10]1[CH2:15][CH:14]=[C:13]([C:16]2[S:17][CH:18]=[CH:19][C:20]=2[O:21][CH3:22])[CH2:12][CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH:31]1([C:37](Cl)=[O:38])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1>ClCCl>[CH2:1]([C@H:8]([NH:23][C:37]([CH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1)=[O:38])[CH2:9][N:10]1[CH2:11][CH:12]=[C:13]([C:16]2[S:17][CH:18]=[CH:19][C:20]=2[O:21][CH3:22])[CH2:14][CH2:15]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 75938Cyclohexanecarbonyl chlorideHCID 15485234HCID 15485234, compound

Product 1

HCID 9954840HCID 9954840, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
4 °C

Procedure

A magnetically stirred solution of 0.5 g (1.52 mmol) of (1S)-1-Benzyl-2-[4-(3-methoxy-thiophen-2-yl)-3,6-dihydro-2H-pyridin-1-yl]-ethylamine and 0.42 ml (3.04 mmol) of triethylamine in 30 ml of dry dichloromethane was cooled in an ice bath under a dry nitrogen atmosphere. A solution of 0.25 g (1.67 mmol) of cyclohexane carbonyl chloride in 6 ml of dry dichloromethane was added dropwise over 10 minutes. The resulting solution was stirred at 4° C. for 1 hour and then the ice bath was removed and stirring was continued overnight (app. 18 hours), during which time the reaction came up to room temperature. TLC on silica gel (4% methanol/dichloromethane) revealed the absence of starting material and a new product (Rf=0.5). The reaction was concentrated on a rotary evaporator and partitioned between 75 ml of ethyl acetate and 50 ml of 1N aqueous sodium hydroxide. The organic layer was dried over anhydrous sodium sulfate and concentrated on a rotary evaporator. The resulting oil was purified by flash chromatography on silica gel (4% methanol/dichloromethane) to give 0.34 g of the desired (S)-cyclohexanecarboxylic acid {1-benzyl-2-[4-(3-methoxy-thiophen-2-yl)-3,6-dihydro-2H-pyridin-1-yl]-ethyl}-amide as oil which hardened upon exposure to vacuum. The compound was converted to its monofumerate·1.25 hydrate salt, yield=0.35 g (41%); mp=194-196° C.; [a]D25 =+5.86 (EtOH, c=0.5).

Workup

  1. customthe ice bath was removed
  2. stirringstirring
  3. waitwas continued overnight
  4. custom(app. 18 hours)
  5. customcame up to room temperature
  6. concentrationThe reaction was concentrated on a rotary evaporator
  7. custompartitioned between 75 ml of ethyl acetate and 50 ml of 1N aqueous sodium hydroxide
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. concentrationconcentrated on a rotary evaporator
  10. customThe resulting oil was purified by flash chromatography on silica gel (4% methanol/dichloromethane)

Sources & evidence

ORD record
ord-86080d159ec944828a06d5ce9509fc1f
Source dataset
uspto-grants-2000_08
Patent number
US06110943

Reaction notes

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