tert-Butanol → Methyl 6-[(tert-butoxycarbonyl)amino]-2-naphthoate

HRID 2238398

Reaction equation

HRID 2238398 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[CH:11]=[C:10](C(O)=O)[CH:9]=[CH:8]2)=[O:4].CC[N:20](CC)CC.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[C:42]([O-:45])(O)=[O:43].[Na+].[CH3:47][C:48](O)([CH3:50])[CH3:49]>>[C:48]([O:45][C:42]([NH:20][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[CH:6]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:14]=[CH:13]2)=[O:43])([CH3:50])([CH3:49])[CH3:47]

Participants

6

Reactant 5

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 516892Sodium BicarbonateHCID 33802176-(Methoxycarbonyl)naphthalene-2-carboxylic acid

Product 1

HCID 44549532Methyl 6-[(tert-butoxycarbonyl)amino]-2-naphthoateYield 78%

Procedure

A suspension of 6-(methoxycarbonyl)-2-naphthoic acid [J. Med. Chem., 2004, 47, 303-324] (146) (1.21 g, 5.26 mmol) in dry t-BuOH (20 mL) containing powdered molecular sieves (1 g) was treated with Et3N (0.88 mL, 6.31 mmol) and stud under N2 at room temperature for 30 min. DPPA (1.25 mL, 5.80 mmol) was added and the mixture was sired at reflux for 7 h, then cooled and poured into dilute aqueous NaHCO3. The resting solid was purified by chromatography on silica gel, eluting with CH2Cl2, followed by trituration with iPr2O and recrystallization from EtOAc to give methyl 6-[(tert-butoxycarbonyl)amino]-2-naphthoate (147) (1.24 g, 78%) as a white solid: mp 178-180° C.; 1H NMR [(CD3)2SO] δ 9.76 (s, 1H), 8.51 (s, 1H), 8.19 (s, 1H), 8.02 (d, J=9.0 Hz, 1H), 7.90 (dd, J=8.6, 1.6 Hz, 1H), 7.86 (d, J=8.7 Hz, 1H), 7.59 (dd, J=8.9, 2.1 Hz, 1H), 3.89 (s, 3H), 1.52 (s, 9H). Anal. (C17H19NO4) C, H, N.

Workup

  1. additioncontaining
  2. temperatureat reflux for 7 h
  3. temperaturecooled
  4. customThe resting solid was purified by chromatography on silica gel
  5. washeluting with CH2Cl2
  6. customfollowed by trituration with iPr2O and recrystallization from EtOAc

Sources & evidence

ORD record
ord-bd1c72b315d944a6b7df28551dc9fefd
Source dataset
uspto-grants-2010_05
Patent number
US07718688B2

Linked notes

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