Triethylamine → 6-(3-Adamantan-1-yl-ureido)-hexanoic acid benzyl ester

HRID 404201Notes

Reaction equation

HRID 404201 reaction equation
[C:1]1([CH3:11])[CH:6]=CC(S(O)(=O)=O)=C[CH:2]=1.[CH2:12]([O:19][C:20](=[O:27])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH2:26])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.ClC(Cl)([O:31]C(=O)OC(Cl)(Cl)Cl)Cl.C(N(CC)CC)C.Cl.Cl.C[N:50]([CH3:59])[C:51]1[CH:58]=[CH:57][C:54](CN)=[CH:53][CH:52]=1>ClCCl>[CH2:12]([O:19][C:20](=[O:27])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:26][C:59]([NH:50][C:51]12[CH2:52][CH:53]3[CH2:54][CH:57]([CH2:11][CH:1]([CH2:6]3)[CH2:2]1)[CH2:58]2)=[O:31])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 27346334-(aminomethyl)-N,N-dimethylaniline dihydrochlorideHCID 13077333Hexanoic acid, 6-amino-, phenylmethyl ester, 4-methylbenzenesulfonate (1:1)

Product 1

HCID 670063306-(3-Adamantan-1-yl-ureido)-hexanoic acid benzyl esterYield 180.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a vigorously stirred suspension of 6-amino-hexanoic acid benzyl ester toluene-4-sulfonic acid (0.786 g, 2.00 mmol) and triphosgene (0.200 g, 0.667 mmol) in dichloromethane (30 mL) at −78° C. under inert atmosphere, was added triethylamine (1.0 mL, 7.188 mmol, in 10 mL dichloromethane) dropwise via additional funnel over a period of 2 hours. The cooling bath was removed and the resulting reaction was allowed to stir at room temperature for 1 hour, after which time, 4-Dimethylaminobenzylamine dihydrochloride (0.303 g, 2.00 mmol) was added to the reaction mixture. After stirring overnight, the mixture was washed with brine (20 mL) and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried over sodium sulfate and the solvent was evaporated. The residue was purified using flash column chromatography (silica gel 60, CH2Cl2/EtOAc=6:1 to 4:1) to afford 6-(3-Adamantan-1-yl-ureido)-hexanoic acid benzyl ester 0.481 g (61% yield). 1H NMR (300 MHz, CDCl3) δ (ppm) 7.34 (m, 5H), 5.11 (s, 2H), 4.61 (t, J=5.7 Hz, 1H), 4.43 (s, 1H), 3.08 (dt, J=6.9, 5.7 Hz, 2H), 2.35 (t, J=7.5 Hz, 2H), 2.04 (m, 3H), 1.94 (m, 6H), 1.65 (m, 8H) 1.46 (m, 2H) 1.31 (m, 2H). 13C NMR (75 MHz, CDCl3) δ (ppm) 173.5, 157.4, 135.9, 128.5, 128.2, 128.1, 66.1, 50.6, 42.5, 39.8, 36.4, 34.1, 29.9, 29.5, 26.4, 24.5.

Workup

  1. customThe cooling bath was removed
  2. customthe resulting reaction
  3. stirringAfter stirring overnight
  4. washthe mixture was washed with brine (20 mL)
  5. extractionthe aqueous layer was extracted with dichloromethane
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. customthe solvent was evaporated
  8. customThe residue was purified

Sources & evidence

ORD record
ord-3e39db3efc644e3c9199fdd1ceb11021
Source dataset
uspto-grants-2014_06
Patent number
US08748463B2

Reaction notes

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