Ethyl Acetate → HCID 67272289, compound

HRID 601704Notes

Reaction equation

HRID 601704 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[C:23]([F:25])[CH:24]=1)[CH2:5][C@H:6]1[C@@H:10]([C@H:11]2[CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][NH:12]2)[O:9][C:8](=[O:21])[NH:7]1.[CH3:26][O:27][C:28]1[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(OCC)(=O)C>C1COCC1.C(O)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[C:23]([F:25])[CH:24]=1)[CH2:5][C@H:6]1[C@@H:10]([C@H:11]2[CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][N:12]2[CH2:32][C:31]2[CH:34]=[CH:35][C:28]([O:27][CH3:26])=[CH:29][CH:30]=2)[O:9][C:8](=[O:21])[NH:7]1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 312444-MethoxybenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 67272110HCID 67272110, compound

Product 1

HCID 67272289HCID 67272289, compoundYield 97.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (4S,5R)-4-(3,5-difluorobenzyl)-5-((R)-1,2,3,4-tetrahydroisoquinolin-3-yl)oxazolidin-2-one (Step A(7), 320 mg, 0.93 mmol) in THF (20 mL) was added 4-methoxybenzaldehyde (253 mg, 1.86 mmol) and acetic acid (2 drops). This mixture was stirred at rt overnight. NaBH(OAc)3 (588 mg, 2.78 mmol) was added and the reaction mixture was stirred at rt for 2 days. Ethyl acetate (300 mL) was added and the mixture was washed with aqueous sodium carbonate, H2O, dried (Na2SO4), and concentrated in vacuo. Crude mixture was purified by silica gel Flash Chromatography to give 420 mg of the title compound (80% yield): 1H NMR (CDCl3, 500 MHz) δ 2.57 (1H, t, J=10 Hz), 2.96 (1H, dd, J=5, 20 Hz), 3.17 (1H, dd, J=5, 15 Hz), 3.44-3.50 (2H, m), 3.68 (2H, dd, J=10, 45 Hz), 3.80 (3H, s), 3.84-3.88 (3H, m), 4.66 (1H, dd, J=5, 10 Hz), 5.29 (1H, s), 6.71-6.74 (3H, m), 6.88 (2H, d, J=10 Hz), 6.98 (1H, d, J=5 Hz), 7.15-7.21 (5H, m). MS (ESI) (M+H)+ 465.12.

Workup

  1. stirringthe reaction mixture was stirred at rt for 2 days
  2. washthe mixture was washed with aqueous sodium carbonate, H2O
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customCrude mixture was purified by silica gel Flash Chromatography

Sources & evidence

ORD record
ord-5be7fed31c794c6ea971ec9b90221d5d
Source dataset
uspto-grants-2011_03
Patent number
US07902218B2

Reaction notes

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