Triethylamine → HCID 59485942, compound

HRID 1972196Notes

Reaction equation

HRID 1972196 reaction equation
[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]3[C@@H:17]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C@H:16]([CH2:24]O)[O:15][C:14]3=[O:26])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.C([N:31](CC)CC)C.S(Cl)(C)(=O)=O.[N-]=[N+]=[N-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]3[C@@H:17]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C@H:16]([CH2:24][NH2:31])[O:15][C:14]3=[O:26])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 24946196HCID 24946196, compound

Product 1

HCID 59485942HCID 59485942, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To (4S,5R)-3-(4-(4-chlorophenoxy)phenyl)-5-(hydroxymethyl)-4-phenyloxazolidin-2-one (44 mg, 0.11 mmol) and triethylamine (0.046 mL, 0.33 mmol) in dichloromethane (1.5 mL) at 0° C. was added mesyl chloride (0.012 mL, 0.15 mmol). The reaction mixture was stirred at this temperature for 20 min until reaction complete as judged by TLC, and then was quenched with NaHCO3 aqueous solution. The aqueous layer was extracted (2× dichloromethane) and the organics combined, dried (MgSO4), and concentrated. The oil was taken up in 2 mL DMF and treated with NaN3 (14 mg, 0.2 mmol) at 70° C. for 5 h (monitored by analytical LC/MS). The reaction was cooled to room temperature, and then quenched with water. Ethyl acetate was added and the organic was washed with brine, dried (MgSO4), and concentrated. The oil was re-dissolved in THF/water (10:1, 1 mL) and treated with triphenylphosphine (34 mg, 0.12 mmol). The reaction was stirred at room temperature overnight and then concentrated. Flash chromatography (0-5% MeOH/dichloromethane) gave 35 mg (80%, 3 steps) of a the title compound as colorless oil that crystallized on standing. 1H NMR (acetone-d6) δ (ppm) 7.49-7.53 (m, 2H), 7.30-7.46 (m, 7H), 6.92-6.97 (m, 4H), 5.48 (d, 1H, J=4.8 Hz), 4.55 (dd, 1H, J=9.5, 4.7 Hz), 3.64 (dd, 2H, J=4.9, 1.6 Hz). HPLC-MS calculated C22H19ClN2O3 (M+H+): 395.1, found: 395.1.

Workup

  1. customwas quenched with NaHCO3 aqueous solution
  2. extractionThe aqueous layer was extracted (2× dichloromethane)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customquenched with water
  6. additionEthyl acetate was added
  7. washthe organic was washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. dissolutionThe oil was re-dissolved in THF/water (10:1, 1 mL)
  11. stirringThe reaction was stirred at room temperature overnight
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-6a4eae3f74f54826813471966e111e2c
Source dataset
uspto-grants-2013_04
Patent number
US08431607B2

Reaction notes

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