Diisopropylethylamine → (S)-2-hydroxy-N-[(S)-6-oxo-5-(2,2,2-trifluoro-ethyl)-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-propionamide

HRID 1374574Notes

Reaction equation

HRID 1374574 reaction equation
[NH2:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([F:14])([F:13])[F:12])[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[C:4]2[CH:19]=[CH:20][CH:21]=[CH:22][C:3]1=2.[C:23](O)(=[O:27])[C@H:24]([CH3:26])[OH:25].O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C.Cl.CN(C)CCCN=C=NCC>O1CCCC1>[OH:25][C@@H:24]([CH3:26])[C:23]([NH:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([F:14])([F:12])[F:13])[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[C:4]2[CH:19]=[CH:20][CH:21]=[CH:22][C:3]1=2)=[O:27]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 107689L-Lactic AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 68848895HCID 68848895, compound

Product 1

HCID 69507821(S)-2-hydroxy-N-[(S)-6-oxo-5-(2,2,2-trifluoro-ethyl)-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-propionamideYield 68.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 0.26 g (0.85 mmol) (S)-7-amino-5-(2,2,2-trifluoro-ethyl)-5H,7H-dibenzo[b,d]azepin-6-one in 18 ml tetrahydrofurane was treated at 0° C. with 0.08 g (0.94 mmol) L-lactic acid, 0.13 g (0.85 mmol) 1-hydroxybenzotriazole hydrate, 297 μl (1.70 mmol) N-ethyldiisopropylamine and 0.17 g (0.85 mmol) N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimid-hydrochlorid. After stirring at room temperature overnight the mixture was extracted with 1N aqueous hydrochloric acid/ethylacetate. Purification by chromatography on silicagel with ethylacetate/heptane (0-100/100-0) yielded 0.22 g (68%) (S)-2-hydroxy-N—[(S)-6-oxo-5-(2,2,2-trifluoro-ethyl)-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-propionamide as grey solid, MS: m/e: 379.4 (M+H+), [α] 589=−23° (1.1% in CHCl3).

Workup

  1. extractionwas extracted with 1N aqueous hydrochloric acid/ethylacetate
  2. customPurification by chromatography on silicagel with ethylacetate/heptane (0-100/100-0)

Sources & evidence

ORD record
ord-c6a0f0e5688f4b96b5deaa190b41bd6a
Source dataset
uspto-grants-2007_01
Patent number
US07166587B2

Reaction notes

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