HCID 59488932, compound → (3-Fluorophenyl)carbamic acid benzyl ester

HRID 2402983Notes

Reaction equation

HRID 2402983 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:12][C@H:11]([CH2:13][N:14]3[CH:18]=[CH:17][N:16]=[N:15]3)[O:10][C:9]2=[O:19])[CH:5]=[CH:4][C:3]=1[C:20]1[CH:25]=[CH:24][C:23]([CH2:26][NH:27][CH2:28][C:29]2[N:30]=[N:31][N:32](CC3C=CC(OC)=CC=3)[CH:33]=2)=[CH:22][CH:21]=1>FC(F)(F)C(O)=O>[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:12][C@H:11]([CH2:13][N:14]3[CH:18]=[CH:17][N:16]=[N:15]3)[O:10][C:9]2=[O:19])[CH:5]=[CH:4][C:3]=1[C:20]1[CH:21]=[CH:22][C:23]([CH2:26][NH:27][CH2:28][C:29]2[N:30]=[N:31][NH:32][CH:33]=2)=[CH:24][CH:25]=1.[CH2:11]([O:10][C:9](=[O:19])[NH:8][C:6]1[CH:5]=[CH:4][CH:3]=[C:2]([F:1])[CH:7]=1)[C:13]1[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1

Participants

4

Reactant 1

HCID 59488932HCID 59488932, compound

Product 2

HCID 895321(3-Fluorophenyl)carbamic acid benzyl esterHCID 178519212HCID 178519212, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
67.5 °C

Procedure

A solution of the crude regioisomeric mixture of (5R)-3-[2-Fluoro-4′-({[1-(4-methoxy-benzyl)-1H-[1,2,3]triazol-4-ylmethyl]-amino}-methyl)-biphenyl-4-yl]-5-[1,2,3]triazol-1-ylmethyl-oxazolidin-2-one (SC-167-71, 0.30 g, 0.528 mmol) in trifluoroacetic acid (TFA, 10 mL) was warmed up to 65-70° C., and the resulting reaction mixture was stirred at 65-70° C. for 12 h. When TLC and HPLC/MS showed that the deprotection reaction was complete, the solvents were removed in vacuo. The residual solids were then treated with ethyl acetate (EtOAc, 10 mL) and H2O (15 mL) before being treated with a saturated aqueous solution of sodium carbonate (30 mL) at room temperature. The resulting mixture was then stirred at room temperature for 1 h before the solids were collected by filtration, washed with EtOAc (2×20 mL) and H2O (2×20 mL), and dried in vacuo at 40-45° C. to afford the crude, (5R)-3-(2-Fluoro-4′-{[(1H-[1,2,3]triazol-4-ylmethyl)-amino]-methyl}-biphenyl-4-yl)-5-[1,2,3]triazol-1-ylmethyl-oxazolidin-2-one (Compound 2 as the free base, 0.18 g, 0.24 g theoretical, 75%) as off-white powders, which by HPLC/MS and 1H NMR was found to be one pure regioisomer. For Compound 2 as the free base: 1H NMR (300 MHz, DMSO-d6) δ 3.71-3.77 (two br. s, 4H, Ar1CH2NHCH2Ar2), 3.93-3.98 (m, 1H), 4.26-4.32 (t, 1H), 4.86 and 4.87 (d, 2H), 5.14-5.22 (m, 1H), 7.35-7.59 (m, 7H, aromatic-H), 7.74 and 7.78 (s, 2H, triazole-CH), 8.19 (s, 1H, triazole-CH); C22H21FN8O2, LCMS (EI) m/e 449 (M++H) and 471 (M++Na).

Workup

  1. customthe resulting reaction mixture
  2. customWhen TLC and HPLC/MS showed that the deprotection reaction
  3. customthe solvents were removed in vacuo
  4. additionThe residual solids were then treated with ethyl acetate (EtOAc, 10 mL) and H2O (15 mL)
  5. additionbefore being treated with a saturated aqueous solution of sodium carbonate (30 mL) at room temperature
  6. stirringThe resulting mixture was then stirred at room temperature for 1 h before the solids
  7. filtrationwere collected by filtration
  8. washwashed with EtOAc (2×20 mL) and H2O (2×20 mL)
  9. customdried in vacuo at 40-45° C.

Sources & evidence

ORD record
ord-0d1bb0b9d9cf4d5f9596da15706fa3fb
Source dataset
uspto-grants-2014_08
Patent number
US08796465B2

Reaction notes

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