Toluene → HCID 102526941, compound

HRID 1056863Notes

Reaction equation

HRID 1056863 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([CH:8]=[CH:9][CH:10]=1)[NH2:7])(=[O:3])[CH3:2].[C:11]1([CH3:17])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Si:18]([O:25][C@H:26]([C@@:28]1([NH:66][C:67]([N:69]([CH3:71])[CH3:70])=[O:68])[C@:33]([OH:35])([CH3:34])[C@@:32]2([CH2:36][O:37][Si:38]([C:51]([CH3:54])([CH3:53])[CH3:52])([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[C@H:30]([O:31]2)[C@@H:29]1[NH:55][C:56](=[O:65])[O:57][CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)[CH3:27])([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]>O.CCOC(C)=O.C(S([O-])(=O)=O)(F)(F)F.C(S([O-])(=O)=O)(F)(F)F.C(S([O-])(=O)=O)(F)(F)F.[Sc+3]>[C:1]([C:4]1[CH:5]=[C:6]([NH:7][C@H:30]2[C@H:29]([NH:55][C:56](=[O:65])[O:57][CH2:58][C:59]3[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=3)[C@:28]([C@@H:26]([O:25][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:19])[CH3:20])[CH3:27])([NH:66][C:67]([N:69]([CH3:70])[CH3:71])=[O:68])[C@:33]([OH:35])([CH3:34])[C@:32]2([CH2:36][O:37][Si:38]([C:51]([CH3:52])([CH3:54])[CH3:53])([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[OH:31])[CH:8]=[CH:9][CH:10]=1)(=[O:3])[CH3:2].[Si:18]([O:25][C@H:26]([C@@:28]1([NH:66][C:67]([N:69]([CH3:71])[CH3:70])=[O:68])[C@:33]([OH:35])([CH3:34])[C@@:32]2([CH2:36][O:37][Si:38]([C:51]([CH3:54])([CH3:52])[CH3:53])([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[C:45]3[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=3)[C@H:30]([O:31]2)[C@@H:29]1[NH:55][C:56](=[O:57])[O:65][CH2:17][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:27])([C:21]([CH3:22])([CH3:23])[CH3:24])([CH3:20])[CH3:19]

Participants

8

Reactant 3

HCID 1140TolueneHCID 74173'-AminoacetophenoneHCID 102526941HCID 102526941, compound

Product 2

HCID 102526941HCID 102526941, compoundYield 18%HCID 102526942HCID 102526942, compound

Reagents, catalysts & solvents 3

HCID 2734571Scandium(III) triflateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

In a nitrogen-filled glove box, a flame-dried 100-mL round-bottomed flask was charged with Sc(OTf)3 (0.38 g, 0.77 mmol, 3.0 equiv). The flask was capped with a rubber septum and removed from the glove box. Toluene (20 mL) was added and to the resulting suspension were added aniline 17 (0.35 g, 2.6 mmol, 10.0 equiv) and a toluene solution (1.5 mL) of epoxide 13 (0.20 g, 0.26 mmol, 1.0 equiv). The reaction was heated to 60° C. with vigorous stirring and maintained for 14 h. (Note: increased reaction times led to product decomposition), The reaction was cooled to rt, diluted with H2O (10 mL) and EtOAc (10 mL), and the resulting mixture was extracted with EtOAc (3×10 mL). The combined organic extracts were washed with 0.5M HCl(aq.) (2×20 mL), saturated NaHCO3(aq.) (15 mL), dried with magnesium sulfate, and concentrated in vacuo. The crude product was purified via flash chromatography (90:10 to 80:20 hexanes:EtOAc) to afford anilino-alcohol 14 as a yellow, viscous oil (0.16 g, 66%) with recovery of the unreacted epoxide 13 (0.04 g, 18%). Analytical data: [α]D19 −39.3 (c=0.70, CHCl3); 1H NMR (600 MHz, CDCl3): δ 8.21 (d, J=6.6 Hz, 1H), 7.70 (d, J=6.6 Hz, 2H), 7.51 (d, J=7.2 Hz, 2H), 7.39 (t, J=7.2 Hz, 1H), 7.32 (t, J=7.2 Hz, 2H), 7.28-7.22 (m, 8H), 7.16 (t, J=7.2 Hz, 2H), 7.12 (t, J=7.8 Hz, 1H), 6.79 (d, J=7.8 Hz, 1H), 6.13 (s, 5.88 (s, 1H), 5.39-5.36 (m, 1H), 5.36 (s, 1H), 5.04 (d, J=12.0 Hz, 1H), 5.01 (d, J=12.0 Hz, 1H), 4.78 (dd, J=4.6, 6.6 Hz, 1H), 4.37 (d, J=10.2 Hz, 1H), 4.13 (s, 1H), 3.68 (dd, J=4.6, 3.0 Hz, 1H), 3.48 (d, J=10.8 Hz, 1H), 2.96 (s, 6H), 2.49 (s, 3H), 1.69 (s, 3H), 1.41 (d, J=6, 6 Hz, 3H), 0.98 (s, 9H), 0.92 (s, 9H), 0.12 (s, 3H), 0.02 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 198.7, 158.6, 158.4, 149.5, 137.7, 136.6, 135.6, 135.4, 132.4, 132.0, 129.6, 128.8, 128.2, 128.1, 127.8, 127.6, 118.2, 117.0, 112.6, 83.6, 81.0, 70.3, 68.4, 66.9, 66.5, 63.0, 59.3, 36.6, 26.7, 26.7, 25.7, 21.2, 19.4, 19.0, 17.7, −4.3, −6.1; LRMS (ESI+) Calcd. for C50H70N8Si2+Na, 933.46. Found, 933.35. IR (thin film, cm−1) 3361, 2953, 2358, 1716, 1698, 1652, 1539, 1488, 1472, 1243, 1041, 829, 701; TLC (80:20 hexanes:EtOAc): Rf=0.35.

Workup

  1. additionIn a nitrogen-filled glove box, a flame-dried 100-mL round-bottomed flask
  2. customThe flask was capped with a rubber septum
  3. customremoved from the glove box
  4. additionToluene (20 mL) was added and to the resulting suspension
  5. temperaturemaintained for 14 h.
  6. temperature(Note: increased reaction times led to product decomposition)
  7. temperatureThe reaction was cooled to rt
  8. extractionthe resulting mixture was extracted with EtOAc (3×10 mL)
  9. washThe combined organic extracts were washed with 0.5M HCl(aq.) (2×20 mL), saturated NaHCO3(aq.) (15 mL)
  10. dry with materialdried with magnesium sulfate
  11. concentrationconcentrated in vacuo
  12. customThe crude product was purified via flash chromatography (90:10 to 80:20 hexanes:EtOAc)

Sources & evidence

ORD record
ord-03cd41840f444e289c49a7797a2edae6
Source dataset
uspto-grants-2016_07
Patent number
US09399652B2

Reaction notes

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