Hydrochloric Acid → N1-(1(S)-benzyl-2-hydroxyethyl)-3(R)-(3-biphenyl-4-yl-1H-pyrrol-1-yl)-N4-hydroxysuccinamide

HRID 613897Notes

Reaction equation

HRID 613897 reaction equation
C([C@H](N[C:12](=[O:35])[C@H:13]([N:18]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:25][CH:24]=2)=[CH:19]1)[CH2:14][C:15](O)=[O:16])CO)C1C=CC=CC=1.CN1[CH2:42][CH2:41][O:40]CC1.Cl.[NH2:44][OH:45].Cl.[NH4+:47].[Cl-]>C(Cl)(Cl)Cl>[CH2:20]([C@H:42]([NH:47][C:15](=[O:16])[CH2:14][C@@H:13]([N:18]1[CH:22]=[CH:21][C:20]([C:23]2[CH:24]=[CH:25][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:27][CH:28]=2)=[CH:19]1)[C:12]([NH:44][OH:45])=[O:35])[CH2:41][OH:40])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 25517Ammonium ChlorideHCID 443297Hydroxyamine hydrochlorideHCID 15459664N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-(3-(biphenyl-4-yl)-1H-pyrrol-yl)succinamic acid

Product 1

HCID 54305058N1-(1(S)-benzyl-2-hydroxyethyl)-3(R)-(3-biphenyl-4-yl-1H-pyrrol-1-yl)-N4-hydroxysuccinamideYield 14%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-(3-(biphenyl-4-yl)-1H-pyrrol-1-yl)succinamic acid (prepared as described in Example 1(a); 61 mg, 0.130 mmol) in CHCl3 (2 mL) was added in succession NMM (44 μL, 0.39 mmol), benzotriazole-1-yloxy-tris-1H-pyrrolidino-phosphonium hexafluorophosphate (PyBOP, 203 mg, 0.390 mmol), and hydroxylamine hydrochloride (27 mg, 0.390 mmol). After 20 hours at ambient temperature, 10% aqueous HCl (2 mL) and saturated aqueous NH4Cl (10 mL) were added, and the resultant mixture extracted with CHCl3 (15 mL) three times. The combined organic layers were washed with saturated aqueous NH4Cl (10 mL), dried over Na2SO4, and evaporated to provide a yellow solid, which was purified via flash column chromatography with 1% HOAc/10% MeOH/CHCl3 as eluant. Subsequent radial chromatography with a 1% HOAc/5-10%MeOH/CH2Cl2 stepwise gradient eluant and azeotropic removal of HOAc with n-heptane gave 9 mg (14%) of N1 -(1(S)-benzyl-2-hydroxyethyl)-3(R)-(3-biphenyl-4-yl-1H-pyrrol-1-yl)-N4 -hydroxysuccinamide as a yellow solid. 1H NMR (CD3OD): ∂ 6.90-6.79 (m, 1H), 6.58-6.76 (m, 1H), 5.18-5.02 (m, 1H), 4.19-4.01 (m, 1H), 3.00-2.84 (m, 1H), 2.84-2.70 (m, 3H). IR (CHCl3): 3244, 3018, 1659, 1208, 1201 cm-1. HRFABMS: Calculated for C29H30N3O4 (M+H+): 483.2158. Found: 483.2139. Anal. Calculated for C29H30N3O4.NH2OH.0.2 CHCl3.0.25 H2O: C, 64.35; H, 6.05; N, 10.28. Found: C, 64.13; H, 5.69; N, 10.56.

Workup

  1. extractionthe resultant mixture extracted with CHCl3 (15 mL) three times
  2. washThe combined organic layers were washed with saturated aqueous NH4Cl (10 mL)
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. customto provide a yellow solid, which
  6. customwas purified via flash column chromatography with 1% HOAc/10% MeOH/CHCl3 as eluant
  7. customSubsequent radial chromatography with a 1% HOAc/5-10%MeOH/CH2Cl2 stepwise gradient eluant and azeotropic removal of HOAc with n-heptane

Sources & evidence

ORD record
ord-24a00666ad1b49c98bdc51f89dfeb549
Source dataset
uspto-grants-1999_12
Patent number
US06008243

Reaction notes

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