Water → HCID 86684916、化合物

HRID 2402911ノート

反応式

HRID 2402911 の反応式
[C:1]([C:3]1([NH:6][C:7]([C@@H:9]2[CH2:13][C@H:12]([OH:14])[CH2:11][N:10]2[C:15]([C:17]2([C:20]([F:23])([F:22])[F:21])[CH2:19][CH2:18]2)=[O:16])=[O:8])[CH2:5][CH2:4]1)#[N:2].[C:24]1([S:30](Cl)(=[O:32])=[O:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(N(CC)CC)C.O>O1CCCC1.CN(C)C1C=CN=CC=1.CO>[C:1]([C:3]1([NH:6][C:7]([C@H:9]2[N:10]([C:15]([C:17]3([C:20]([F:23])([F:21])[F:22])[CH2:19][CH2:18]3)=[O:16])[CH2:11][C@@H:12]([O:14][S:30]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)(=[O:32])=[O:31])[CH2:13]2)=[O:8])[CH2:4][CH2:5]1)#[N:2]

参加物

8

反応物 4

HCID 962WaterHCID 7369Benzenesulfonyl chlorideHCID 8471TriethylamineHCID 86684901HCID 86684901、化合物

生成物 1

HCID 86684916HCID 86684916、化合物収率 99%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

(2S,4S)-4-Hydroxy-1-(1-trifluoromethyl-cyclopropanecarbonyl)-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amide (100.0 g, 301.8 mmol) was dissolved in tetrahydrofuran (500 mL). The mixture was cooled to 2° C. (ice bath), benzenesulfonyl chloride (99%, 48 mL, 370.5 mmol), 4-(dimethylamino)pyridine (98%, 2.0 g, 16.0 mmol), and triethylamine (75.0 mL, 539 mmol) were added subsequently and the mixture was stirred for 15 min. The reaction was allowed to warm to room temperature and stirred for 20 h. After cooling to 2° C. (ice bath), water (150 mL) and methanol (350 mL) were added. Tetrahydrofuran was distilled off carefully in vacuo (ca. 500 mL) and water (500 mL) was added slowly. After addition of 300 mL water, crystallization was induced by addition of seed crystals. The resulting suspension was stirred for 30 min at 2° C. (ice bath) and filtered. The solid was washed with methanol/water 1:2 (v/v, 300 mL) and heptane (300 mL) and dried in vacuo to afford the title compound as off-white crystals (140.8 g, 99%). 1H NMR (CDCl3, 400 MHz): δ 1.06-1.27 (m, 4H), 1.28-1.41 (m, 2H), 1.44-1.54 (m, 2H), 2.26 (ddd, J=5.9 Hz, 9.4 Hz, 14.2 Hz, 1H), 2.59 (ddd, J=3.8 Hz, 3.8 Hz, 14.2 Hz, 1H), 3.90 and 4.03 (ABX, JAB=12.5 Hz, JAx=4.0 Hz, JBX=5.2 Hz, each 1H), 4.57 (br d, J=5.1 Hz, 1H), 5.02-5.09 (m, 1H), 7.08 (br s, 1H), 7.61 (t, J=7.8 Hz, 2H), 7.71 (t, J=7.5 Hz, 1H), 7.95 (d, J=7.2 Hz, 2H).

後処理

  1. additionwere added subsequently
  2. stirringstirred for 20 h
  3. additionwere added
  4. distillationTetrahydrofuran was distilled off carefully in vacuo (ca. 500 mL) and water (500 mL)
  5. additionwas added slowly
  6. additionAfter addition of 300 mL water, crystallization
  7. additionwas induced by addition of seed crystals
  8. stirringThe resulting suspension was stirred for 30 min at 2° C. (ice bath)
  9. filtrationfiltered
  10. washThe solid was washed with methanol/water 1:2 (v/v, 300 mL) and heptane (300 mL)
  11. customdried in vacuo

出典と根拠

ORDレコード
ord-2c592608c45d4a84a9acd08af469a294
出典データセット
uspto-grants-2014_08
特許番号
US08796471B2

反応ノート

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