Diisopropylethylamine → HCID 22286093, compound

HRID 1062287Notes

Reaction equation

HRID 1062287 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=2[CH3:19])[CH:3]=1.C(N(C(C)C)CC)(C)C.[C:29]([Si:33]([CH3:41])([CH3:40])[O:34][CH2:35][CH2:36][CH2:37][O:38][NH2:39])([CH3:32])([CH3:31])[CH3:30].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>ClCCl.CCOCC>[C:29]([Si:33]([CH3:40])([CH3:41])[O:34][CH2:35][CH2:36][CH2:37][O:38][NH:39][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([F:1])=[CH:3][C:4]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=1[CH3:19])([CH3:32])([CH3:31])[CH3:30]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 9820737HCID 9820737, compoundHCID 22286275O-(3-((tert-Butyldimethylsilyl)oxy)propyl)hydroxylamine

Product 1

HCID 22286093HCID 22286093, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4-fluoro-2-(4-iodo-2-methyl-phenylamino)benzoic acid (3.32 g, 8.95 mmol) in dichloromethane at ambient temperature was added diisopropylethylamine (2.82 mL, 16.2 mmol). To the resultant solution was added O-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-hydroxylamine (2.19 g, 10.65 mmol) and PyBOP. After 1.5 h of stirring, the solution was diluted with ether (100 mL) and was washed with water (3×50 mL) and brine (50 mL), dried over magnesium sulfate and filtered, and concentrated in vacuo to obtain a gum. Chromatographed the gum using a gradient of 100% hexanes to 30% ethyl acetate in hexanes over 45 min. The solvent of the combined fractions was removed in vacuo to obtain a yellow gum. The gum was dried on a vacuum pump for c. a. 18 h which afforded N-[3-(tert -Butyl-dimethyl-silanyloxy)-propoxy]-4-fluoro-2-(4-iodo-2-methyl-phenylamino)-benzamide as a solid. (4.06 g, 81% yield). 1H-NMR (400 MHz, CDCl3) δ 9.3 (br. s., 1H), 9.0 (br. s., 1H), 7.58 (s, 1H), 7.49 (dd, 1H, J=8.3, 1.95 Hz)), 7.36 (br. t., 1H,=5.71 Hz), 7.05 (d, 1H, J=8.3 Hz), 6.65 (dd, 1H, J=11.96, 2.44 Hz), 6.4 (br. t., J=7.1 Hz), 4.14 (t, 2H, J=5.61 Hz), 3.812 (t, 2H, J=5.62 Hz), 2.28 (s, 3H), 1.94 (p, 2H, J=5.86 Hz), 0.9 (s, 9H), 0.08 (s, 6H). 19F-NMR (376 MHz, CDCl3) δ −105.25. MS (AP+) 559.2 m/z, (AP−) 557.1 m/z.

Workup

  1. washwas washed with water (3×50 mL) and brine (50 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto obtain a gum
  6. customChromatographed the gum
  7. customover 45 min
  8. customThe solvent of the combined fractions was removed in vacuo
  9. customto obtain a yellow gum
  10. customThe gum was dried on a vacuum pump for c

Sources & evidence

ORD record
ord-de1f63ebe20244e6acdb72126deaba85
Source dataset
uspto-grants-2005_11
Patent number
US06960614B2

Reaction notes

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