tert-Butanol → Tert-butyl 6-cyano-2-naphthylcarbamate

HRID 2238392

Reaction equation

HRID 2238392 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8](C(O)=O)[CH:7]=[CH:6]2)#[N:2].CC[N:18]([CH2:21]C)CC.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:30])=CC=1.[CH3:40][C:41]([OH:44])([CH3:43])[CH3:42]>>[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([NH:18][C:21](=[O:30])[O:44][C:41]([CH3:43])([CH3:42])[CH3:40])[CH:7]=[CH:6]2)#[N:2]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 124330906-Cyanonaphthalene-2-carboxylic acid

Product 1

HCID 44549529Tert-butyl 6-cyano-2-naphthylcarbamateYield 74%

Procedure

A suspension of 6-cyano-2-naphthoic acid [J. Med. Chem., 2004, 47, 303-324] (139) (4.62 g, 23.4 mmol) in dry t-BuOH (120 mL) containing powdered molecular sieves (2 g) was treated with Et3N (3.91 mL, 28.1 mmol) and the mixture was stirred at room temperature under N2 for 30 min. DPPA (5.55 mL, 25.8 mmol) was added, and the mixture was stirred at reflux for 6 h, then concentrated to half volume and poured into dilute aqueous NaHCO3. The resulting solid was purified by chromatography on silica gel, eluting with CH2Cl2, to give tert-butyl 6-cyano-2-naphthylcarbamate (140) (4.68 g, 74%): mp (MeOH/H2O) 135-136° C.; 1H NMR [(CD3)2SO] δ 9.85 (s, 1H), 8.42 (d, J=0.9 Hz, 1H), 8.23 (d, J=1.0H, 1H), 7.95 (d, J=8.7H, 2H), 7.68 (dd, J=8.5, 1.6 Hz, 1H), 7.64 (dd, J=9.0, 2.0 Hz, 1H), 1.52 (s, 9H). Anal. (C16H16N2O2) C, H, N.

Workup

  1. additioncontaining
  2. stirringthe mixture was stirred
  3. temperatureat reflux for 6 h
  4. concentrationconcentrated to half volume
  5. additionpoured into dilute aqueous NaHCO3
  6. customThe resulting solid was purified by chromatography on silica gel
  7. washeluting with CH2Cl2

Sources & evidence

ORD record
ord-3e552ca8e3894f208b57401cbecdf0ca
Source dataset
uspto-grants-2010_05
Patent number
US07718688B2

Linked notes

Loading…