Hydrochloric Acid → (S)-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)-N,N,3,3-tetramethylbutanamide

HRID 537374ノート

反応式

HRID 537374 の反応式
[CH3:1][N:2]([CH3:18])[C:3](=[O:17])[C@@H:4]([NH:9]C(=O)OC(C)(C)C)[C:5]([CH3:8])([CH3:7])[CH3:6].Cl.CCN(CC)CC.[F:27][C:28]([F:43])([F:42])[C:29]1[CH:30]=[C:31]([N:39]=[C:40]=[S:41])[CH:32]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=1>O1CCOCC1>[F:36][C:35]([F:37])([F:38])[C:33]1[CH:32]=[C:31]([NH:39][C:40](=[S:41])[NH:9][C@@H:4]([C:5]([CH3:8])([CH3:7])[CH3:6])[C:3]([N:2]([CH3:18])[CH3:1])=[O:17])[CH:30]=[C:29]([C:28]([F:42])([F:27])[F:43])[CH:34]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 27333953,5-Bis(trifluoromethyl)phenyl isothiocyanateHCID 57635614(S)-tert-butyl 1-(dimethylamino)-3,3-dimethyl-1-oxobutan-2-ylcarbamate

生成物 1

HCID 24859431(S)-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)-N,N,3,3-tetramethylbutanamide収率 71.5%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

A 50-mL round-bottomed flask was charged with (S)-tert-butyl 1-(dimethylamino)-3,3-dimethyl-1-oxobutan-2-ylcarbamate (6c) (860 mg, 2.0 mmol, 1.0 equiv) and 4N HCl in dioxane (5.0 mL). The reaction mixture was stirred at room temperature for 2 h, then concentrated under reduced pressure and maintained at ˜1 torr for 1 h. The resulting white, foamy solid was dissolved in CH2Cl2 (10 mL). Et3N (562 μL, 4.0 mmol, 2.0 equiv) and 3,5-bis(trifluoromethyl)phenylisothiocyanate (596 mg, 2.2 mmol, 1.1 equiv) were added sequentially via syringe. The flask was capped with a plastic stopper, and the reaction mixture was stirred at room temperature for 14 h. The reaction mixture was concentrated under reduced pressure, and the residue was subjected to purification by flash column chromatography on silica gel (gradient elution, 3:1 hexanes/Et2O→1:1 hexanes/Et2O) to provide the product (4a) as a white solid (613 mg, 1.43 mmol, 71% yield over two steps). [α]D25=−32.8° (c 1.0, CHCl3). 1H NMR (500 MHz, CDCl3): δ 9.06 (1H, s), 7.90 (2H, s), 7.77 (1H, d, J=9 Hz), 7.56 (1H, s), 5.68 (1H, d, J=9 Hz), 3.35 (3H, s), 2.97 (3H, s), 1.12 (9H, s). 13C {1H}NMR (100 MHz, CDCl3): δ 181.8, 174.0, 140.3, 131.7 (q, JC-F=33 Hz), 123.7 (m), 123.3 (q, JC-F=272 Hz), 118.1 (m), 60.9, 39.1, 36.2, 36.0, 27.2. IR (cm−1): 3322 (br m), 2972 (m), 1611 (m), 1532 (s), 1474 (m), 1385 (m), 1274 (s), 1174 (m), 1126 (s), 963 (m), 883 (m), 848 (w), 700 (m), 680 (m). LRMS (ESI): 452.1 (60%) [M+Na]+.

後処理

  1. concentrationconcentrated under reduced pressure
  2. temperaturemaintained at ˜1 torr for 1 h
  3. dissolutionThe resulting white, foamy solid was dissolved in CH2Cl2 (10 mL)
  4. customThe flask was capped with a plastic stopper
  5. stirringthe reaction mixture was stirred at room temperature for 14 h
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. customthe residue was subjected to purification by flash column chromatography on silica gel (gradient elution, 3:1 hexanes/Et2O→1:1 hexanes/Et2O)

出典と根拠

ORDレコード
ord-9ce3dfc5a80c4b82a5508945739497fd
出典データセット
uspto-grants-2014_10
特許番号
US08859812B2

反応ノート

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