Ethyl Acetate → HCID 25010231, compound

HRID 2093161Notes

Reaction equation

HRID 2093161 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=3Br)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:31][O:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]2[CH:44]=[CH:43][C:42]([C:45]([O:47][CH3:48])=[O:46])=[CH:41][C:40]=2[CH3:49])=[CH:35][C:34]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Na+].[Na+].CCOC(C)=O>O.CCO.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCCCCC>[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=3[C:34]3[CH:35]=[C:36]([C:39]4[CH:44]=[CH:43][C:42]([C:45]([O:47][CH3:48])=[O:46])=[CH:41][C:40]=4[CH3:49])[CH:37]=[CH:38][C:33]=3[O:32][CH3:31])[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 57692976HCID 57692976, compound2×HCID 86620317(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-bromo-5-chlorobenzyl)-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 25010231HCID 25010231, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8058HexaneSolventHCID 86587398Ethanol toluene waterSolvent

Procedure

A mixture of the title compound from Step B (0.068 g, 0.13 mmol), methyl 4′-methoxy-2-methyl-3′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-4-carboxylate (INTERMEDIATE 11) (0.075 g, 0.19 mmol), tetrakis(triphenylphosphine)palladium (15 mg, 5% mol) and sodium carbonate (0.07 g, 0.65 mmol) in 7 ml of water/EtOH/toluene (1:2:4) was heated to reflux for 5 h. TLC (EtOAc:hexane/1:3) showed that the reaction was over. The solvents were removed. Water (10 ml) was added. The organic was extracted with methylene chloride (3×20 ml). The combined methylene chloride layers were washed with brine, and dried over sodium sulfate. The title compound was obtained after purification with preparative TLC using 10% EtOAc in hexane as the eluant. 1H NMR (CDCl3, 500 MHz): δ 1:1 mixture of atropisomers 7.96 (d, J=9 Hz, 1H), 7.88(m, 2H), 7.72(s, 1H), 7.65(s, 1H), 7.49 (d, J=2 Hz, 0.5H), 7.39 (m, 2H), 7.36 (d, J=2 Hz, 0.5H), 7.24-7.28 (m, 2H), 7.15 (m, 1H), 7.70 (m, 1H), 5.62 (d, J=8 Hz, 0.5H), 5.52(d, J=8 Hz, 0.5H), 4.91(t, J=16 Hz, 1H), 4.08(d, J=15.5 Hz, 0.5H), 3.95(s, 3H), 3.88 (s, 3H), 3.87(d, J=16 Hz, 0.5H), 3.84 (m, 1H), 2.39(s, 1.5H), 2.33(s, 1.5H), 0.56(d, J=7 Hz, 1.5H), 0.43(d, J=6.5 Hz, 1.5H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 5 h
  3. customThe solvents were removed
  4. additionWater (10 ml) was added
  5. extractionThe organic was extracted with methylene chloride (3×20 ml)
  6. washThe combined methylene chloride layers were washed with brine
  7. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-1a5c02807c584113a9ced97fa27eb50b
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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