1-Hydroxybenzotriazole → HCID 59511125, compound

HRID 1774258Notes

Reaction equation

HRID 1774258 reaction equation
[F:1][C:2]1([CH2:10][C:11]2[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[CH:13][CH:12]=2)[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][C:4]#[C:3]1.FC(F)(F)C([O-])=O.[O:27]=[C:28]1[CH:32]=[CH:31][C:30](=[O:33])[N:29]1[CH2:34][CH2:35][CH2:36][NH3+:37].ON1C2C=CC=CC=2N=N1>C(Cl)Cl>[O:27]=[C:28]1[CH:32]=[CH:31][C:30](=[O:33])[N:29]1[CH2:34][CH2:35][CH2:36][NH:37][C:15](=[O:17])[C:14]1[CH:13]=[CH:12][C:11]([CH2:10][C:2]2([F:1])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][C:4]#[C:3]2)=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 757711-HydroxybenzotriazoleHCID 59511126HCID 59511126, compoundHCID 67388280HCID 67388280, compound

Product 1

HCID 59511125HCID 59511125, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TEA (0.508 mL, 3.65 mmol) was added to a solution of cyclooctyne 3b (0.200 g, 0.768 mmol), amine 13 (0.235 g, 0.875 mmol), O-(7-Azabenzotriazol-1-yl)-N,N,N′,N-tetramethyluronium hexafluorophosphate (HATU, 0.305 g, 0.802 mmol), and 1-hydroxybenzotriazole (HOBT, 0.123 g, 0.802 mmol) in CH2Cl2 (3 mL) at rt. The reaction was stirred for 15 min at rt, quenched with H2O (10 mL), and diluted with CH2Cl2 (50 mL). The organic layer was washed with 1 N HCl (3×50 mL), saturated NaHCO3 (3×50 mL), and brine (2×25 mL) and dried over MgSO4. Chromatography of the crude product (2:1 to 1:1 hexanes/EtOAc) yielded the desired product as a white solid (0.198 g, 65%, Rf=0.30 in 1:1 hexanes/EtOAc), mp 122.0-124.0° C. (dec). IR: 3413, 2931, 2854, 2222, 1705, 1640 cm−1. 1H NMR (CDCl3, 400 MHz): δ 1.39 (m, 1H), 1.74 (m, 2H), 1.81-2.06 (m, 6H), 2.14-2.32 (m, 3H), 3.05 (d, 1H, J=2.8 Hz), 3.09 (s, 1H), 3.40 (q, 2H, J=6.4 Hz), 3.67 (t, 2H, J=6.0 Hz), 6.75 (s, 2H), 6.93 (m, 1H), 7.41 (d, 2H, J=8.0 Hz), 7.81 (d, 2H, J=8.0 Hz). 13C NMR (CDCl3, 100 MHz): δ 20.5, 26.0, 28.1, 29.4, 34.0, 34.8, 36.2, 44.6 (d, J=25.0 Hz), 47.8 (d, J=24.0 Hz), 90.7 (d, J=32.0 Hz), 95.3 (d, J=174.0 Hz), 104.5 (d, J=10.0 Hz), 126.7, 130.5, 132.9, 134.2, 139.6, 167.1, 171.1. 19F NMR (CDCl3, 376 MHz): δ −139.0 (m). FAB-HRMS: Calcd. for C23H26N2O3F+ [M+H]+: 397.1927. found: 397.1920.

Workup

  1. customquenched with H2O (10 mL)
  2. additiondiluted with CH2Cl2 (50 mL)
  3. washThe organic layer was washed with 1 N HCl (3×50 mL), saturated NaHCO3 (3×50 mL), and brine (2×25 mL)
  4. dry with materialdried over MgSO4

Sources & evidence

ORD record
ord-ee062272f1e940f0983fcb7bfbded64d
Source dataset
uspto-grants-2016_02
Patent number
US09260371B2

Reaction notes

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