Hydroxyamine hydrochloride → methyl (2S)-2-[(4-tert-butylbenzoyl)amino]-3-[4-[(Z)-N'-hydroxycarbamimidoyl]phenyl]propanoate

HRID 1775803Notes

Reaction equation

HRID 1775803 reaction equation
[C:1]([C:5]1[CH:27]=[CH:26][C:8]([C:9]([NH:11][C@@H:12]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[CH:20][CH:19]=2)[C:13]([O:15][CH3:16])=[O:14])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:29][OH:30]>CCO>[C:1]([C:5]1[CH:27]=[CH:26][C:8]([C:9]([NH:11][C@@H:12]([CH2:17][C:18]2[CH:23]=[CH:22][C:21](/[C:24](=[N:29]/[OH:30])/[NH2:25])=[CH:20][CH:19]=2)[C:13]([O:15][CH3:16])=[O:14])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 73939388(S)-methyl 2-(4-(tert-butyl)benzamido)-3-(4-cyanophenyl)propanoate

Product 1

HCID 89620330methyl (2S)-2-[(4-tert-butylbenzoyl)amino]-3-[4-[(Z)-N'-hydroxycarbamimidoyl]phenyl]propanoateYield 95.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
85 °C

Procedure

Prepared using General Procedure 2: To a stirring solution (S)-methyl 2-(4-(tert-butyl)benzamido)-3-(4-cyanophenyl)propanoate (1.0 g, 2.74 mmol) in EtOH (15 mL) were added hydroxylamine hydrochloride (572.2 mg, 8.22 mmol) and TEA (1.38 g, 13.7 mmol). The reaction was heated to 85° C. for 2 h. The solvent was removed under reduced pressure and the residue was diluted with water (20 mL) and extracted with DCM (3×10 mL). The combined organic layers were concentrated under reduced pressure. The crude material was crystallized from isopropanol (20 mL) to afford 1.04 g (95%) of (S,Z)-methyl 2-(4-(tert-butyl)benzamido)-3-(4-(N′-hydroxycarbamimidoyl)phenyl)propanoate (INT-2) as a white solid. LCMS-ESI (m/z): calcd for: C22H27N3O4, 397.2. found 398.1 [M+H]+, tR=2.26 min (Method 1). 1H NMR (400 MHz, DMSO) δ 10.19 (s, 1H), 9.57 (s, 1H), 8.78 (d, J=7.9 Hz, 1H), 7.74 (d, J=8.4 Hz, 2H), 7.58 (d, J=8.2 Hz, 2H), 7.48 (d, J=8.4 Hz, 2H), 7.30 (d, J=8.3 Hz, 2H), 4.79-4.49 (m, 1H), 3.65 (s, 3H), 3.15 (dt, J=13.6, 6.0 Hz, 2H), 1.75 (d, J=13.6 Hz, 1H), 1.29 (s, 9H).

Workup

  1. customPrepared
  2. customThe solvent was removed under reduced pressure
  3. additionthe residue was diluted with water (20 mL)
  4. extractionextracted with DCM (3×10 mL)
  5. concentrationThe combined organic layers were concentrated under reduced pressure
  6. customThe crude material was crystallized from isopropanol (20 mL)

Sources & evidence

ORD record
ord-0bd8118971e54879a85c47d41d8f8742
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

Loading…