3,5-Bis(trifluoromethyl)phenyl isothiocyanate → HCID 44477827, 화합물

HRID 537373노트

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HRID 537373 반응식
[NH2:1][C@@H:2]([C:20]([CH3:23])([CH3:22])[CH3:21])[C:3]([N:5]([CH:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH3:6])=[O:4].[F:24][C:25]([F:40])([F:39])[C:26]1[CH:27]=[C:28]([N:36]=[C:37]=[S:38])[CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1>C(Cl)Cl>[CH:7]([N:5]([CH3:6])[C:3](=[O:4])[C@@H:2]([NH:1][C:37]([NH:36][C:28]1[CH:29]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:31]=[C:26]([C:25]([F:24])([F:39])[F:40])[CH:27]=1)=[S:38])[C:20]([CH3:23])([CH3:22])[CH3:21])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

참가 물질

4

반응물 2

HCID 27333953,5-Bis(trifluoromethyl)phenyl isothiocyanateHCID 71293931(S)-2-amino-N-benzhydryl-N,3,3-trimethylbutanamide

생성물 1

HCID 44477827HCID 44477827, 화합물수율 92%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A 100-mL round-bottomed flask containing (S)-2-amino-N-benzhydryl-N,3,3-trimethylbutanamide (6b) (2.98 g, 9.60 mmol, 1.0 equiv) was charged with anhydrous CH2Cl2 (30 mL). 3,5-Bis(trifluoromethyl)phenylisothiocyanate (1.75 mL, 9.60 mmol, 1.0 equiv) was added in one portion via syringe. The flask was capped with a plastic stopper, and the reaction mixture was stirred for 2 h at room temperature. The clear, yellow solution was concentrated using a rotary evaporator. The residue was subjected to purification by flash column chromatography on silica gel (gradient elution, hexanes→1:1 hexanes/Et2O, 100 g silica gel, 1.5 L solvent). The product (4e) was isolated as a white solid in ˜98% 1H-NMR purity (5.14 g, 8.83 mmol, 92% yield; 74% yield over three steps). The compound exists as a 15:1 mixture of amide rotamers in CDCl3. [α]=−83.4° (c 1.0, CHCl3). 1H NMR (500 MHz, CDCl3), major rotamer: δ 8.26 (1H, br s), 8.92 (1H, br s), 7.69 (2H, s), 7.59 (1H, s), 7.31-7.37 (3H, m), 7.13-7.16 (2H, m), 6.95-7.06 (5H, m), 5.65 (1H, d, J=9 Hz), 3.13 (3H, s), 1.13 (9H, s); selected minor rotamer resonances: δ 2.76 (3H, s), 0.92 (9H, s). 13C {1H} NMR, major rotamer: δ 182.5, 174.2, 139.7, 139.0, 137.3, 131.9 (q, JC-F=34 Hz), 129.8, 128.8, 128.7, 128.4, 128.2, 127.5, 127.2, 126.3 (m), 123.1 (q, JC-F=274 Hz), 119.3 (m), 62.4, 62.3, 36.5, 34.0, 27.6. IR (cm−1): 3313 (br m), 2967 (m), 1609 (m), 1529 (m), 1473 (m), 1380 (m), 1276 (s), 1172 (m), 1127 (s), 961 (m), 889 (w), 847 (w), 758 (w), 698 (m), 681 (m). LRMS (ESI): 582.2 (80%) [M+H].

후처리

  1. customThe flask was capped with a plastic stopper
  2. concentrationThe clear, yellow solution was concentrated
  3. customa rotary evaporator
  4. customThe residue was subjected to purification by flash column chromatography on silica gel (gradient elution, hexanes→1:1 hexanes/Et2O, 100 g silica gel, 1.5 L solvent)

출처 및 근거

ORD 기록
ord-093a3912e294422a8ca0b4164dfc61d0
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08859812B2

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