Triethylamine → {(1R)-1-{(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethylcarbamoyl}-2-(2-naphthyl)ethyl}carbamic acid tertbutyl ester

HRID 849823Notes

Reaction equation

HRID 849823 reaction equation
Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.[C:24]([O:28][C:29]([NH:31][C@H:32]([C:44]([OH:46])=O)[CH2:33][C:34]1[CH:43]=[CH:42][C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:35]=1)=[O:30])([CH3:27])([CH3:26])[CH3:25].Cl.[CH3:48][C:49]1[N:53]=[C:52]([CH:54]([NH2:62])[CH2:55][C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)[O:51][N:50]=1.C(N(CC)CC)C>CN(C)C=O>[C:24]([O:28][C:29](=[O:30])[NH:31][C@@H:32]([C:44](=[O:46])[NH:62][C@@H:54]([C:52]1[O:51][N:50]=[C:49]([CH3:48])[N:53]=1)[CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[CH2:33][C:34]1[CH:43]=[CH:42][C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:35]=1)([CH3:26])([CH3:27])[CH3:25]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 7020908Boc-3-(2-naphthyl)-L-alanineHCID 225924571-(3-Methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethylamine hydrochloride

Product 1

HCID 54237827{(1R)-1-{(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethylcarbamoyl}-2-(2-naphthyl)ethyl}carbamic acid tertbutyl esterYield 80.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (6.3 g, 32.9 mmol) and 1-hydroxybenzotriazole monohydrate (5.0 g, 32.9 mmol) were added to a solution of (R) N-tert-butoxycarbonyl-3-(2-naphthyl)-alanine (10.4 g, 32.9 mmol) in N,N-dimethylformamide (140 ml). After 1 h at 20° C. a mixture of 1-(3-methyl-[1,2,4]oxadiazole-5-yl)-2-phenylethylamine hydrochloride (5.6 g, 23.5 mmol) and triethylamine (2.37 g, 23.5 mmol) in N,N-dimethylformamide (100 ml) were added. After 18 h at 20° C. the reaction mixture was poured onto water (1.4 L) and extracted several times with ethyl acetate (total 1.4 L). The combined organic phases were washed with aqueous citric acid (10%, 200 ml), a saturated solution of sodium hydrogencarbonate (200 ml) and water (3×200 ml). After drying (magnesium sulfate) the solution was concentrated in vacuo and crystallized from ethyl acetate and heptane to give 9.45 g of {(1R)-1-{(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethylcarbamoyl}-2-(2-naphthyl)ethyl}carbamic acid tertbutyl ester.

Workup

  1. additionwere added
  2. additionAfter 18 h at 20° C. the reaction mixture was poured onto water (1.4 L)
  3. extractionextracted several times with ethyl acetate (total 1.4 L)
  4. washThe combined organic phases were washed with aqueous citric acid (10%, 200 ml)
  5. dry with materialAfter drying (magnesium sulfate) the solution
  6. concentrationwas concentrated in vacuo
  7. customcrystallized from ethyl acetate and heptane

Sources & evidence

ORD record
ord-be82460fc76a4733ae397d81183c5359
Source dataset
uspto-grants-2000_01
Patent number
US06013658

Reaction notes

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