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

HRID 1784954Notes

Reaction equation

HRID 1784954 reaction equation
[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]

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-05def82bb6244609805478b31b3662e3
Source dataset
uspto-grants-2009_03
Patent number
US07504425B2

Reaction notes

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