6,8-Difluoro-2-tetralone → 2-(6,8-Difluoro-1,2,3,4-tetrahydro-naphthalen-2-ylamino)-pentanoic acid methyl ester

HRID 553178Notes

Reaction equation

HRID 553178 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:10])[C@H:5]([CH2:7][CH2:8][CH3:9])[NH2:6].[F:11][C:12]1[CH:13]=[C:14]2[C:19](=[C:20]([F:22])[CH:21]=1)[CH2:18][C:17](=O)[CH2:16][CH2:15]2.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:2][O:3][C:4](=[O:10])[CH:5]([NH:6][CH:17]1[CH2:16][CH2:15][C:14]2[C:19](=[C:20]([F:22])[CH:21]=[C:12]([F:11])[CH:13]=2)[CH2:18]1)[CH2:7][CH2:8][CH3:9]

Participants

5

Reactant 3

HCID 40764316,8-Difluoro-2-tetraloneHCID 5049666Sodium triacetoxyborohydrideHCID 14118488methyl (2S)-2-aminopentanoate hydrochloride

Product 1

HCID 671643272-(6,8-Difluoro-1,2,3,4-tetrahydro-naphthalen-2-ylamino)-pentanoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Combine L-norvaline methyl ester-hydrochloride (1 equiv) with 6,8-difluoro-3,4-dihydro-1H-naphthalen-2-one (1 equiv) in methylene chloride and stir 30 min. and add sodium triacetoxy borohydride (1.1 equiv) and stir at rt overnight. The reaction is quenched with aqueous sodium bicarbonate, extracted with methylene chloride, dried, and concentrated. The resultant material is purified by silica gel chromatography to afford the separated diastereomers of 2-(6,8-Difluoro-1,2,3,4-tetrahydro-naphthalen-2-ylamino)-pentanoic acid methyl ester: Diastereomer 1; 13C NMR (100 MHz, CDCl3) 14.0, 19.4, 27.7, 28.2, 29.5, 29.6, 36.3, 51.1, 58.7, 100.7, 100.9, 101.2, 110.5, 110.7, 110.8, 118.5, 118.6, 141.1, 159.7, 159.8, 162.1, 176.7; MS m/z 298.3 (M+1). Diastereomer 2; Diagnostic 13C NMR (100 MHz, CDCl3) 14.0, 19.3, 28.3, 28.4, 28.5, 30.3, 36.4, 51.1, 52.0, 58.5, 100.7, 100.9, 101.2, 110.5, 110.7, 176.8; MS m/z 298.3 (M+1).

Workup

  1. customThe reaction is quenched with aqueous sodium bicarbonate
  2. extractionextracted with methylene chloride
  3. customdried
  4. concentrationconcentrated
  5. customThe resultant material is purified by silica gel chromatography

Sources & evidence

ORD record
ord-b84c76259d384df3afa674c658456489
Source dataset
uspto-grants-2011_05
Patent number
US07951958B2

Reaction notes

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