Triethylamine → 2-Chloro-5-(3-hydroxypropyl)-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide

HRID 1593810Notes

Reaction equation

HRID 1593810 reaction equation
C(OC(Cl)=O)C(C)C.C(N(CC)CC)C.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][C:25](O)=[O:26])=[CH:19][C:18]=1[C:28]([NH:30][CH2:31][C:32]12[CH2:41][CH:36]3[CH2:37][CH:38]([CH2:40][CH:34]([CH2:35]3)[CH2:33]1)[CH2:39]2)=[O:29]>O1CCCC1>[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][CH2:25][OH:26])=[CH:19][C:18]=1[C:28]([NH:30][CH2:31][C:32]12[CH2:41][CH:36]3[CH2:35][CH:34]([CH2:40][CH:38]([CH2:37]3)[CH2:39]1)[CH2:33]2)=[O:29]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 129886864-Chloro-3-[[(tricyclo[3.3.1.13,7]dec-1-ylmethyl)amino]carbonyl]-benzenepropanoic acid

Product 1

HCID 129886872-Chloro-5-(3-hydroxypropyl)-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamideYield 82.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Isobutylchloroformate (0.575 ml) and triethylamine (0.63 ml) were added to a solution of 4-chloro-3-[[(tricyclo[3.3.1.13,7]dec-1-ylmethyl)amino]carbonyl]-benzenepropanoic acid (Example 6c, 1.64 g) in tetrahydrofuran (30 ml) at 0° C. After 1 h the precipitates were removed by filtration and the filtrate added portionwise to a solution of sodium borohydride (0.18 g) in water (10 ml) at 0° C. After a further 1 h the reaction mixture was poured onto dilute hydrochloric acid and extracted with ethyl acetate. The organic phase was extracted twice with dilute hydrochloric acid, twice with saturated sodium hydrogencarbonate solution and once with brine, dried over magnesium sulfate and concentrated under reduced pressure to give a residue. Purification by silica gel chromatography (eluting with dichloromethane/methanol 96:4); yielded the subtitled compound as a solid (1.3 g).

Workup

  1. customAfter 1 h the precipitates were removed by filtration
  2. additionthe filtrate added portionwise to a solution of sodium borohydride (0.18 g) in water (10 ml) at 0° C
  3. additionAfter a further 1 h the reaction mixture was poured onto dilute hydrochloric acid
  4. extractionextracted with ethyl acetate
  5. extractionThe organic phase was extracted twice with dilute hydrochloric acid, twice with saturated sodium hydrogencarbonate solution and once with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customto give a residue
  9. customPurification
  10. washby silica gel chromatography (eluting with dichloromethane/methanol 96:4)

Sources & evidence

ORD record
ord-c50680288a7646398807fef9fd53393e
Source dataset
uspto-grants-2007_11
Patent number
US07297818B2

Reaction notes

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