Isopropanol → HCID 54035099, compound

HRID 2288765Notes

Reaction equation

HRID 2288765 reaction equation
[C:1]([N:11]1[CH2:18][C@@H:17]2[C@@H:13]([CH2:14][N:15]([C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:29][C@@H:28]([CH2:30]CS([O-])(=O)=O)[O:27][C:26]4=[O:36])=[CH:21][C:20]=3[F:37])[CH2:16]2)[CH2:12]1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C1COCC1.C(O)(C)C.[OH-].[NH4+:48]>C(Cl)Cl>[C:1]([N:11]1[CH2:12][C@@H:13]2[C@@H:17]([CH2:16][N:15]([C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:29][C@H:28]([CH2:30][NH2:48])[O:27][C:26]4=[O:36])=[CH:21][C:20]=3[F:37])[CH2:14]2)[CH2:18]1)([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 8028TetrahydrofuranHCID 14923Ammonium HydroxideHCID 86755528HCID 86755528, compound

Product 1

HCID 54035099HCID 54035099, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
95 °C

Procedure

To a flame dried flask equipped with a nitrogen inlet is introduced (R)-[3-[4-[cis-3-(carbobenzyloxy)-3,7-diazabicyclo[3.3.0]octan-7-yl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methanol (1.75 g, 3.84 mmol) and methylene chloride (100 mL) cooled to 0° C. Triethylamine (0.80 mL, 5.76 mmol) and methanesulfonyl chloride are added, stirred at 0° C. for 2 hours, and warmed to ambient temperature for 1 hour. The reaction is washed with water (30 mL), saturated sodium bicarbonate (30 mL), and saline (30 mL), dried over sodium sulfate, and concentrated in vacuo to give the crude (R)-[[3-[4-[cis-3-(carbobenzyloxy)-3,7-diazabicyclo[3.3.0]octan-7-yl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]methanesulfonate. (R)-[[3-[4-[cis-3-(Carbobenzyloxy)-3,7-diazabicyclo[3.3.0]octan-7-yl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]methanesulfonate is combined in a resealable tube with THF (5 mL), isopropanol (5 mL), and concentrated ammonium hydroxide (10 mL) and heated to 95° C. for 10 hours. The reaction is diluted with methylene chloride (50 mL) and washed with saline (30 mL), dried over sodium sulfate, concentrated in vacuo to give (S)-[[3-[4-[cis-3-(carbobenzyloxy)-3,7-diazabicyclo[3.3.0]octan-7-yl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]amine. The crude (S)-[[3-[4-[cis-3-(carbobenzyloxy)-3,7-diazabicyclo[3.3.0]octan-7-yl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]amine (1.67 g, 3.67 mmol) is dissolved in methylene chloride (20 mL), cooled to 0° C. under nitrogen, pyridine (0.89 mL, 11.02 mmol) and acetic anhydride (0.43 mL, 4.59 mmol) are added, and the reaction is stirred 15 hours at ambient temperature. The reaction is diluted with methylene chloride (50 mL), washed with 1N HCl (25 mL), saturated sodium bicarbonate (25 mL), saline (25 mL), dried over sodium sulfate, concentrated in vacuo, and chromatographed on silica gel (230-400 mesh, 200 mL), eluting with chloroform/methanol (98/2). The appropriate fractions are combined (Rf =0.15, TLC, chloroform/methanol, 95/5) and concentrated in vacuo to give the title compound, mp 165-168° C.

Workup

  1. washwashed with saline (30 mL)
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1b11c6c74502461688150e4415acbe37
Source dataset
uspto-grants-2000_07
Patent number
US06090820

Reaction notes

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