Benzyl bromoacetate → HCID 22861554, compound

HRID 865284Notes

Reaction equation

HRID 865284 reaction equation
[O:1]=[C:2]([N:40]1[C@@H:44]([CH:45]([CH3:47])[CH3:46])[CH2:43][O:42][C:41]1=[O:48])[C@H:3]([CH2:15][C:16]1[N:17]=[CH:18][N:19]([C:21]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:20]=1)[CH2:4][C:5](=[O:14])[O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].BrCC(OCC1C=CC=CC=1)=O>C1COCC1>[O:1]=[C:2]([N:40]1[C@@H:44]([CH:45]([CH3:46])[CH3:47])[CH2:43][O:42][C:41]1=[O:48])[CH:3]([CH2:15][C:16]1[N:17]=[CH:18][N:19]([C:21]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:20]=1)[CH2:4][C:5](=[O:14])[O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 62576Benzyl bromoacetateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 22866493HCID 22866493, compound

Product 1

HCID 22861554HCID 22861554, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

3-{1,4-Dioxo-4-(phenylmethoxy)-2(R)-{[1-triphenylmethyl-1H-imidazol-4-yl]methyl}butyl}-4(S)-(1-methylethyl)-2-oxazolidinone: A 1.0M solution of sodium bis(trimethylsilyl)amide (18.0 mL, 18.0 mmol, Aldrich Chemical Co., Inc., Milwaukee, Wis. USA) was added dropwise (18 min) to a cold (-78° ) solution of the product of the preceding section (8.06 g, 16.3 mmol) in THF (65 mL). After 40 min at -78° , a solution of benzyl 2-bromoacetate (7.48 g, 32.7 mmol) in THF (2 mL) was added dropwise to the solution. The reaction mixture was stirred at -78° for 1.5 h, quenched with an aqueous saturated solution of NH4Cl, allowed to warm to room temperature and then poured into a mixture of H2O (500 mL) and aqueous saturated solution of NH4Cl (100 mL). The resulting mixture was extracted with EtOAc. The EtOAc extract was washed with a saturated aqueous solution of NaHCO3 and then brine, dried (MgSO4) and concentrated under reduced pressure to give 3-{1,4-dioxo-4-(phenylmethoxy)-2{[1-(triphenylmethyl)-1H-imidazol-4-yl]methyl}butyl}-4(S)-(1-methylethyl)-2-oxazolidinone as a mixture of 2(R)- and 2(S)-epimers in a 8 to 1 ratio by weight. Separation of the epimers by flash chromatography (SiO2, eluent: hexane-EtOAc, 1:2) yielded the desired 2(R)-epimer (Rf=0.25, eluent: hexane-EtOAc,1:2). The 1H NMR (CDCl3) of the 2(R)-epimer showed δ7.34-7.28 (m,15H), 7.13-7.08 (m,6H) 6.59 (d, J=1.3 Hz, 1H), 5.06 (s,2H), 4.55-4.45 (m, 1H), 4.38 (td, J=3.9 Hz, 5.4 Hz, 1H), 4.15-4.10 (m,2H), 2.97 (dd, J=10.3 Hz, 16.9 Hz, 1H), 2.88 (dd J=6.3 Hz, 14.3 Hz, 1H), 2.73 (dd, J=7.0 Hz, 14.3 Hz 1H), 2.59 (dd, J=4.4 Hz, 16.9 Hz, 1H), 2.32 (hept d, J=3.9 Hz, 7.0 Hz, 1H), 0.87 (d, J=7.1 Hz, 3H) 0.85 (d, J=6.8 Hz, 3H).

Workup

  1. customquenched with an aqueous saturated solution of NH4Cl
  2. additionpoured into a mixture of H2O (500 mL) and aqueous saturated solution of NH4Cl (100 mL)
  3. extractionThe resulting mixture was extracted with EtOAc
  4. extractionThe EtOAc extract
  5. washwas washed with a saturated aqueous solution of NaHCO3
  6. dry with materialbrine, dried (MgSO4)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5d5eea05a8ff43b3809b879a36a4d996
Source dataset
uspto-grants-1996_10
Patent number
US05565476

Reaction notes

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