tert-Butanol → HCID 69480388, compound

HRID 2364127Notes

Reaction equation

HRID 2364127 reaction equation
[CH3:1][CH2:2][O:3][C:4]([C:6]1[C:11](C(O)=O)=[CH:10][C:9]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)=[CH:8][N:7]=1)=[O:5].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:30])C=CC=CC=1.CC[N:42]([CH2:45]C)CC.[CH3:47][C:48]([OH:51])([CH3:50])[CH3:49]>>[F:22][C:19]1[CH:18]=[CH:17][C:16]([CH2:15][C:9]2[CH:10]=[C:11]([NH:42][C:45]([O:51][C:48]([CH3:50])([CH3:49])[CH3:47])=[O:30])[C:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])=[N:7][CH:8]=2)=[CH:21][CH:20]=1

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 42637769HCID 42637769, compound

Product 1

HCID 69480388HCID 69480388, compound

Procedure

A solution of 5-(4-fluorobenzyl)-2,3-pyridinedicarboxylic acid 2-ethyl ester (28 g, 92 mmol), diphenylphosphoryl azide (29.7 mL, 138 mmol) and Et3N (38.5 mL, 276 mmol) in t-BuOH (250 mL) was heated at reflux for 5 h and stored at rt for 3 d. After removal of solvent in vacuo, EtOAc was added and the mixture was washed with NH4Cl solution, NaHCO3 solution and brine, and then dried and concentrated. The crude material was purified by column chromatography on silica gel eluting with 30% EtOAc/hexanes to afford the product as the major isomer. This material contained ca. 30% of the corresponding 3-ethyl ester 2-(tert-butoxy)carbonylamino isomer. Major isomer: 1H NMR (d6-DMSO) δ 9.96 (1H, s), 8.30 (1H, d, J=2 Hz), 8.24 (1H, d, J=2 Hz), 7.27 (2H, m), 7.11 (2H, m), 4.28 (2H, q, J=7 Hz), 4.01 (2H, s), 1.43 (9H, s), 1.28 (3H, t, J=7 Hz); AP+ MS: 375 (M+H+, 100).

Workup

  1. temperatureat reflux for 5 h
  2. customAfter removal of solvent in vacuo, EtOAc
  3. additionwas added
  4. washthe mixture was washed with NH4Cl solution, NaHCO3 solution and brine
  5. customdried
  6. concentrationconcentrated
  7. customThe crude material was purified by column chromatography on silica gel eluting with 30% EtOAc/hexanes
  8. customto afford the product as the major isomer

Sources & evidence

ORD record
ord-2088aee290e1402c80841de7b95fafb8
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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