4-Methylmorpholine → HCID 10717338, compound

HRID 1953051Notes

Reaction equation

HRID 1953051 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@H:15]2[C:19](=[O:20])[NH:18][C@@H:17]([C:21]([OH:23])=O)[CH2:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CC[O:28][CH2:27][CH2:26]1.Cl.[CH3:32][Si:33](C)([CH3:38])[CH2:34]CON.B(F)([O-])[O-].B(F)([O-])[O-].B(F)([O-])[O-].B(F)([O-])[O-].B(F)([O-])[O-].B(F)([O-])[O-].[N:64]1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl>[CH3:32][Si:33]([CH3:38])([CH3:34])[CH2:26][CH2:27][O:28][NH:64][C:21]([C@H:17]1[CH2:16][C@@H:15]([C:12]2[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[CH:10][CH:11]=2)[C:19](=[O:20])[NH:18]1)=[O:23]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 10828821HCID 10828821, compoundHCID 18419632O-[2-(Trimethylsilyl)ethyl]hydroxylamine--hydrogen chloride (1/1)HCID 86755729HCID 86755729, compound

Product 1

HCID 10717338HCID 10717338, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2R, 4S)-4-(4-benzyloxyphenyl)-5-oxo-pyrrolidine-2-carboxylic acid (330 mg, 1.06 mmol), N-methyl morpholine (0.25 mL, 2.3 mmol) and O-(2-trimethylsilylethyl) hydroxylamine hydrochloride (220 mg, 1.30 mmol) in CH2Cl2 (20 mL) was added (benztriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluoroborate (560 mg, 1.27 mmol). The reaction was stirred at room temperature for 6 hours. After dilution with CH2Cl2, the mixture was washed sequentially with aqueous 0.5M HCl solution, water, aqueous saturated NaHCO3 solution, and brine. The solution was dried over MgSO4 and concentrated to a white solid that was triturated with ethyl acetate and set aside. The trituration filtrate was concentrated and chromatographed on silica gel eluting with 5% methanol in chloroform. Fractions containing the title compound were combined and concentrated to afford a white solid that was combined with the solid obtained directly from the crude product mixture. The sample was stirred in water overnight. The title compound was collected by filtration and dried. The yield was 194 mg (43%).

Workup

  1. washAfter dilution with CH2Cl2, the mixture was washed sequentially with aqueous 0.5M HCl solution, water, aqueous saturated NaHCO3 solution, and brine
  2. dry with materialThe solution was dried over MgSO4
  3. concentrationconcentrated to a white solid
  4. customthat was triturated with ethyl acetate
  5. concentrationThe trituration filtrate was concentrated
  6. customchromatographed on silica gel eluting with 5% methanol in chloroform
  7. additionFractions containing the title compound
  8. concentrationconcentrated
  9. customto afford a white solid

Sources & evidence

ORD record
ord-9ddf5a22371345b9ad2ee675e82c375b
Source dataset
uspto-grants-2000_09
Patent number
US06114361

Reaction notes

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