1,2-Dichloroethane → N-t-butoxy-2(R)-[(4-fluoro-3-methylphenylsulfonyl)]amino-3-methylbutyramide

HRID 1784954ノート

反応式

HRID 1784954 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C@H:12]([CH:16]([CH3:18])[CH3:17])[C:13]([OH:15])=O)(=[O:10])=[O:9])=[CH:4][C:3]=1[CH3:19].CCN(C(C)C)C(C)C.Cl.[C:30]([O:34][NH2:35])([CH3:33])([CH3:32])[CH3:31].CCN=C=NCCCN(C)C.Cl.C(Cl)CCl>C(Cl)Cl>[C:30]([O:34][NH:35][C:13](=[O:15])[C@H:12]([NH:11][S:8]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[C:3]([CH3:19])[CH:4]=1)(=[O:9])=[O:10])[CH:16]([CH3:18])[CH3:17])([CH3:33])([CH3:32])[CH3:31]

参加物

7

反応物 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2777906O-tert-butylhydroxylamine hydrochlorideHCID 422557322(R)-[(4-Fluoro-3-methylphenylsulfonyl)]amino-3-methylbutyric acid

生成物 1

HCID 86599433N-t-butoxy-2(R)-[(4-fluoro-3-methylphenylsulfonyl)]amino-3-methylbutyramide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

2(R)-[(4-Fluoro-3-methylphenylsulfonyl)]amino-3-methylbutyric acid (2.64 g, 9.12 mmol) was dissolved in DCM (30 ml), followed by addition of DIEA (3.18 ml, 2 eq.) and O-t-butylhydroxylamine hydrochloride (2.3 g, 2 eq.). EDC.HCl (2.1 g, 1.2 eq.) was then added portionwise as solid. More EDC (0.6, 0.5 eq.) was added after 40 min and the reaction was stirred for another 30 min. The solvent was removed on a rotavap at room temperature, and residue was partitioned with ethylacetate (80 ml), 1N HCl (50 ml). The organic layer was washed with 1N HCl, brine, and dried over Na2SO4. The crude product was flash column purified with 5% to 12% ethylacetate in DCM gradient solvent to give product N-t-butoxy-2(R)-[(4-fluoro-3-methylphenylsulfonyl)]amino-3-methylbutyramide as a white foam. TLC (1:10 ethylaceate:DCM) Rf 0.16. NMR (500 MHz, CD3OD) δ: 0.89 (d, 3H), 0.90 (d, 3H), 1.08 (s, 9H), 1.86 (m, 1H), 2.30 (d, 3H), 3.44 (d, 1H), 7.18 (t, 1H), 7.70 (m, 1H), 7.77 (m, 1H).

後処理

  1. customThe solvent was removed on a rotavap at room temperature
  2. customresidue was partitioned with ethylacetate (80 ml), 1N HCl (50 ml)
  3. washThe organic layer was washed with 1N HCl, brine
  4. dry with materialdried over Na2SO4
  5. custompurified with 5% to 12% ethylacetate in DCM gradient solvent

出典と根拠

ORDレコード
ord-05def82bb6244609805478b31b3662e3
出典データセット
uspto-grants-2009_03
特許番号
US07504425B2

反応ノート

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