Dichloromethane → 3-(4-(3(S)-Acetamidopyrrolidin-1-yl)-3-fluorophenyl)-5(R)-(N-(2,2,2-trichloro-ethyloxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one

HRID 1582346Notes

Reaction equation

HRID 1582346 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][N:20]([C:29]4[CH:33]=[CH:32][O:31][N:30]=4)[C:21]([O:23][CH2:24][C:25]([Cl:28])([Cl:27])[Cl:26])=[O:22])[O:16][C:15]3=[O:34])=[CH:10][C:9]=2[F:35])[CH2:4]1.C(=O)(O)[O-].[Na+].ClCCl.[C:44](OC(=O)C)(=[O:46])[CH3:45]>O>[C:44]([NH:2][C@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][N:20]([C:29]4[CH:33]=[CH:32][O:31][N:30]=4)[C:21]([O:23][CH2:24][C:25]([Cl:28])([Cl:26])[Cl:27])=[O:22])[O:16][C:15]3=[O:34])=[CH:10][C:9]=2[F:35])[CH2:4]1)(=[O:46])[CH3:45]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 7918Acetic Anhydride2×HCID 516892Sodium BicarbonateHCID 695849253-(4(3(S) aminopyrrolidin-1-yl)-3-fluorophenyl)-5(R)-(N-(2,2,2-trichloroethyloxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one hydrochloride salt

Product 1

HCID 695847253-(4-(3(S)-Acetamidopyrrolidin-1-yl)-3-fluorophenyl)-5(R)-(N-(2,2,2-trichloro-ethyloxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-oneYield 83.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

3-(4-(3(S)-Aminopyrrolidin-1-yl)-3-fluorophenyl)-5(R)-(N-(2,2,2-trichloroethyloxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one hydrochloride salt (400 mg, 0.74 mM) was dissolved in water (5 ml) and treated with aqueous sodium bicarbonate solution (5 ml) and dichloromethane (10 ml) in an ice-bath. Acetic anhydride (216 mg, 2 mM) was added, the mixture stirred 18 hours, allowing the temperature to rise to ambient, followed by addition of a further portion of acetic anhydride (216 mg ), and a further period of 10 hours stirring. The organic phase was separated, washed with aqueous sodium dihydrogen phosphate (2%, 2×15 ml), brine (10 ml), and dried (magnesium sulfate). Evaporation gave the desired product (338 mg ). NMR (DMSO-d6) δ: 1.79 (s overlapping m, 4H); 2.11 (hextet, 1H); 3.11 (m, 1H); 3.26 (m overlapped by H2O, ˜1H); 3.40 (dd, 1H); 3.49 (m, 1H); 3.8.2 (dd, 1H); 4.13 (t overlapping dd, 2H); 4.27 (dd, 1H); 4.35 (dd, 1H); 4.97 (d, 1H); 5.01 (m, 1H); 5.07 (d, 1H); 6.73 (t, 1H); 6.88 (d, 1H); 7.08 (dd, 1H); 7.35 (dd, 1H); 8.08 (d, 1H); 8.89 (d, 1H). MS (ESP): 578 (MH+) for C22H23Cl3FN5O6

Workup

  1. stirringa further period of 10 hours stirring
  2. customThe organic phase was separated
  3. washwashed with aqueous sodium dihydrogen phosphate (2%, 2×15 ml), brine (10 ml)
  4. dry with materialdried (magnesium sulfate)
  5. customEvaporation

Sources & evidence

ORD record
ord-836511a16a1c467a8d7a02096119dda0
Source dataset
uspto-grants-2004_05
Patent number
US06734200B1

Reaction notes

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