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Diisopropylethylamine → (+/-)-4-[(3,3-Dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoic acid ethyl ester

HRID 1424256
ノート
印刷プレビュー

反応式

HRID 1424256 の反応式
[CH2:1]([O:3][C:4](=[O:19])[C:5]1[CH:10]=[CH:9][C:8]([CH:11]([NH2:18])[CH:12]2[CH2:15][C:14]([CH3:17])([CH3:16])[CH2:13]2)=[CH:7][CH:6]=1)[CH3:2].[CH3:20][C:21]1[CH:22]=[N+:23]([O-])[C:24]2[C:29]([CH:30]=1)=[CH:28][CH:27]=[CH:26][CH:25]=2.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1>ClCCl>[CH2:1]([O:3][C:4](=[O:19])[C:5]1[CH:10]=[CH:9][C:8]([CH:11]([CH:12]2[CH2:13][C:14]([CH3:16])([CH3:17])[CH2:15]2)[NH:18][C:22]2[C:21]([CH3:20])=[CH:30][C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=2)=[CH:7][CH:6]=1)[CH3:2]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 70214663-Methylquinoline N-oxideHCID 71243808(+/-)-4-[Amino-(3,3-dimethyl-cyclobutyl)-methyl]-benzoic acid ethyl ester2 回

生成物 1

HCID 71243836(+/-)-4-[(3,3-Dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoic acid ethyl ester収率 64.3%

試薬・触媒・溶媒

1
HCID 6344Dichloromethane溶媒

実験手順

(+/−)-4-[amino-(3,3-dimethyl-cyclobutyl)-methyl]-benzoic acid ethyl ester (Intermediate 24) (45 mg, 0.17 mmol) was combined with 3-methylquinoline-N-oxide (27.4 mg, 0.172 mmol, Alfa Aesar, Ward Hill, Mass., USA) and dichloromethane (2 mL). Diisopropylethylamine (0.112 mL, 0.645 mmol) was added followed by bromotripyrrolidinophosphonium hexafluorophosphate (109 mg, 0.224 mmol). The solution was stirred at room temperature for 28 h before partitioning between ethyl acetate and aq. sat. NaHCO3. The separated aqueous layer was extracted with additional ethyl acetate and the combined organics dried over MgSO4. Purification by silica gel flash chromatography (ethyl acetate/heptane) gave (+/−)-4-[(3,3-dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoic acid ethyl ester (44.0 mg) as a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J=8.4 Hz, 2H) 7.56-7.62 (m, 2H) 7.46-7.53 (m, 3H) 7.38-7.46 (m, 1H) 7.12-7.20 (m, 1H) 5.33 (dd, J=9.5, 6.7 Hz, 1H) 4.77 (d, J=6.6 Hz, 1H) 4.34 (q, J=7.2 Hz, 2H) 2.67 (sxt, J=8.8 Hz, 1H) 2.30 (s, 3H) 1.97 (ddd, J=11.1, 8.1, 3.2 Hz, 1H) 1.74-1.85 (m, 1H) 1.66-1.73 (m, 2H) 1.36 (t, J=7.1 Hz, 3H) 1.16 (s, 3H) 1.10 (s, 3H); MS (M+1): 403.3.

後処理

  1. custombefore partitioning between ethyl acetate and aq. sat. NaHCO3
  2. extractionThe separated aqueous layer was extracted with additional ethyl acetate
  3. dry with materialthe combined organics dried over MgSO4
  4. customPurification by silica gel flash chromatography (ethyl acetate/heptane)

出典と根拠

ORDレコード
ord-c6c17c969ae14836ae470b8d4db33e5c
出典データセット
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08927577B2

反応ノート

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