Benzyl Alcohol → HCID 59375144, compound

HRID 1811150Notes

Reaction equation

HRID 1811150 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[F:26])=[C:8]2[C:16]=1[NH:15][C:14]1[CH:13]=[C:12](C(O)=O)[CH:11]=[CH:10][C:9]2=1)(=[O:3])[NH2:2].C1(P([N:41]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.[C:44]1([CH2:50][OH:51])[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.[O:52]1[CH2:57]COCC1>>[C:1]([C:4]1[CH:5]=[CH:6][C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[F:26])=[C:8]2[C:16]=1[NH:15][C:14]1[CH:13]=[C:12]([NH:41][C:57](=[O:52])[O:51][CH2:50][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[CH:11]=[CH:10][C:9]2=1)(=[O:3])[NH2:2]

Participants

5

Reactant 4

HCID 244Benzyl AlcoholHCID 312751,4-DioxaneHCID 199401P,P-Diphenylphosphinic azideHCID 59375023HCID 59375023, compound

Product 1

HCID 59375144HCID 59375144, compoundYield 83%

Conditions

Temperature
50 °C

Procedure

A suspension of 8-carbamoyl-5-(2-fluorophenyl)-9H-carbazole-2-carboxylic acid (Example 23-2, 320 mg, 0.919 mmol) and 4 Å molecular sieves (60 mg) in 1,4-dioxane (15 mL) at 50° C. was treated with TEA (0.316 mL, 2.269 mmol) and diphenylphosphoryl azide (0.491 mL, 2.269 mmol). The mixture was stirred at 50° C. for 1.5 h, followed by addition of phenylmethanol (0.951 mL, 9.19 mmol). The mixture was then stirred at 80° C. for 18 h. The cooled mixture was partitioned between EtOAc and NaHCO3 (aq). The organic phase was washed with brine, dried and concentrated The residue was purified by column chromatography (eluting with 35:65 hexane-EtOAc). The residue after concentration was suspended in hexane and the precipitate was collected by filtration to provide benzyl 8-carbamoyl-5-(2-fluorophenyl)-9H-carbazol-2-ylcarbamate as an off-white solid (400 mg, 83%). 1H NMR (400 MHz, DMSO-d6) δ 11.50 (s, 1 H) 9.83 (s, 1 H) 8.15 (br. s., 1 H) 8.00 (s, 1 H) 7.91 (d, J=7.69 Hz, 1 H) 7.45-7.64 (m, 3 H) 7.32-7.46 (m, 7 H) 7.03 (d, J=7.91 Hz, 1 H) 6.87-6.98 (m, 2 H) 5.15 (s, 2 H). Mass spectrum m/z 454.1 (M+H)+.

Workup

  1. stirringThe mixture was then stirred at 80° C. for 18 h
  2. customThe cooled mixture was partitioned between EtOAc and NaHCO3 (aq)
  3. washThe organic phase was washed with brine
  4. customdried
  5. concentrationconcentrated The residue
  6. customwas purified by column chromatography (eluting with 35:65 hexane-EtOAc)
  7. concentrationThe residue after concentration
  8. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-eeb6b567d33d4c99aae7b64821672915
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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