Ethanol → HCID 59252970, compound

HRID 884749Notes

Reaction equation

HRID 884749 reaction equation
C(O/[C:4](=[C:6]1/C(=O)O[C:9](=[O:17])[C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]/1=2)/[CH3:5])C.[C:19]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])(=[O:22])[NH:20][NH2:21].C(O)C>>[C:24]([O:23][C:19](=[O:22])[NH:20][N:21]1[C:4]([CH3:5])=[CH:6][C:11]2[C:10](=[C:15]([F:16])[CH:14]=[CH:13][CH:12]=2)[C:9]1=[O:17])([CH3:27])([CH3:26])[CH3:25]

Participants

4

Reactant 3

HCID 702EthanolHCID 70091tert-Butyl carbazateHCID 58525654HCID 58525654, compound

Product 1

HCID 59252970HCID 59252970, compoundYield 63.7%

Procedure

A suspension of 4-[1-Ethoxy-eth-(E)-ylidene]-8-fluoro-2-benzopyran-1,3-dione (5.25 g, 21.0 mmol), tert-butyl carbazate (3.43 g, 26.0 mmol) in ethanol (25.0 mL, 428 mmol) was heated under reflux for 30 min with intensive gas formation. The obtained clear purple solution was allowed to cool to r.t. with formation of white precipitate, cooled on dry ice—ethanol bath, filtered, washed with cold ethanol (3×10 ml) to give 3.436 g of the pure title product. Supernatant was quenched with water (200 ml), sat. aq. NaHCO3 (50 ml) and diisopropyl ether (ca 20 ml), shaked, then quenched with heptane (100 ml) and sonicated. White precipitated was separated from this bilayer system by filtration to give 470 mg more of the title product; total yield 63.7%. LC-MS (m/z) 293.0 (traces, MH+), fragments: 237.3, 193.2 (major, M-Boc), 176.3. 1H NMR (500 MHz, DMSO-d6), 88:12 mixture of rotamers A and B: 1.29 (s, 1.1H, tBu of B), 1.47 (s, 7.9H, tBu of A), 2.21 (s, 2.6H, Me of A), 2.21 (s, 0.4H, Me of B), 6.52 (s, 1H, C4-H), 7.17 (dd, J=8.3 Hz, J (H—F)=11.6 Hz, 1H, C7-H), 7.36 (d, J=7.9 Hz, 1H, C5-H), 7.68 (dt, J=7.8 Hz, J (H—F)=4.9 Hz, 1H, C6-H), 9.33 (s, 0.12H, NH of B), 9.8 (s, 0.88H, NH of A). 13C APT NMR (125.76 MHz, dmso-d6=39.89 ppm): 18.96 (Me), 27.99 (tBu of B), 28.31 (tBu of A), 80.98 (C of tBu), 103.59 (C4-H), 112.81 (d, J=20.9 Hz, C7-H), 113.25 (d, J=5 Hz, C9), 122.03 (d, J=3.5 Hz, C5-H), 134.62 (d, J=9.9 Hz, C6-H), 139.64 (C10), 143.96 (C3), 155.39 (NHCO2), 157.88 (d, J=4.5 Hz, C1=O), 161.77 (d, J=262 Hz, C8-F). 19F NMR (470.59 MHz): −111.47 (unres. dd, J=11 Hz, J<4 Hz, rotamer A), −111.35 (unres. dd, J=10.5 Hz, rotamer B). VT 1H NMR (T=353 K, 250 MHz): all doubled signals corresponding to rotamers A and B have coalesced.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 30 min with intensive gas formation
  3. temperaturecooled on dry ice—ethanol bath
  4. filtrationfiltered
  5. washwashed with cold ethanol (3×10 ml)

Sources & evidence

ORD record
ord-3c932ecc31c641beada41ab544bdefd5
Source dataset
uspto-grants-2012_08
Patent number
US08242134B2

Reaction notes

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