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Benzyl Isothiocyanate → N-(((3S,4R,5S)-3-(2,3-difluorophenyl)-4-(hydroxymethyl)-5-((trityloxy)methyl)tetrahydrofuran-3-yl)carbamothioyl)benzamide

HRID 707704
ノート
印刷プレビュー

反応式

HRID 707704 の反応式
[C:1]([C@@](C(O)=O)(O)[C@@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:27][C@@:28]1([C:56]2[CH:61]=[CH:60][CH:59]=[C:58]([F:62])[C:57]=2[F:63])[CH2:32][O:31][C@H:30]([CH2:33][O:34][C:35]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C@H:29]1[CH2:54][OH:55].[OH-].[Na+].C([N:73]=[C:74]=[S:75])C1C=CC=CC=1>CCOC(C)=O>[F:63][C:57]1[C:58]([F:62])=[CH:59][CH:60]=[CH:61][C:56]=1[C@@:28]1([NH:27][C:74]([NH:73][C:1](=[O:8])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[S:75])[C@H:29]([CH2:54][OH:55])[C@@H:30]([CH2:33][O:34][C:35]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)([C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)[C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[O:31][CH2:32]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 2346Benzyl IsothiocyanateHCID 14798Sodium HydroxideHCID 131733709((2S,3R,4S)-4-amino-4-(2,3-difluorophenyl)-2-((trityloxy)methyl)tetrahydrofuran-3-yl)methanol (-)dibenzoyl-L-tartaric acid

生成物 1

HCID 60169626N-(((3S,4R,5S)-3-(2,3-difluorophenyl)-4-(hydroxymethyl)-5-((trityloxy)methyl)tetrahydrofuran-3-yl)carbamothioyl)benzamide収率 100.9%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒2 回

反応条件

温度
1.7000000476837158 °C

実験手順

A suspension of ((2S,3R,4S)-4-amino-4-(2,3-difluorophenyl)-2-((trityloxy)methyl)tetrahydrofuran-3-yl)methanol (−)dibenzoyl-L-tartaric acid (44.21 g, 0.051 mol, 1.0 equiv.) in EtOAc (133 mL) was cooled down to 1.7° C. Aq. NaOH (1.0 M, 121 mL, 0.12 mol, 2.4 equiv.) was added while maintaining temperature below 5° C. The reaction was stirred for 5 min then benzyl isothiocyanate (9.43 g, 0.058 mol, 1.12 equiv.) was added over 5 min. After 1.5 h, EtOAc (133 mL) was added. The organic phase was isolated and successively washed with saturated aq. NaHCO3 (130 mL) and 18% aq.NaCl (44 mL). The combined aqueous phases were extracted with EtOAc (66 mL) and CH2Cl2 (30 mL). All the organic phase were combined, filtered and concentrated under reduced pressure. The title compound (34.2 g) was isolated as a foam after chasing the residual solvent with CH2Cl2 (88 mL). 1H NMR (500 MHz, DMSO) δ ppm 11.97 (br s, 1H), 11.20 (br s, 1H), 7.94 (d, J=7.4 Hz, 2H), 7.63 (t, J=7.4 Hz, 1H), 7.51 (t, J=7.8 Hz, 2H), 7.38-7.21 (m, 17H), 7.13 (dd, J=13.4, 7.9 Hz, 1H), 5.13 (t, J=4.4 Hz, 1H), 5.07 (d, J=9.7 Hz, 1H), 4.47 (d, J=9.8 Hz, 1H), 4.24-4.16 (m, 1H), 3.68 (t, J=4.6 Hz, 2H), 3.19 (dd, J=10.1, 2.9 Hz, 1H), 3.01 (dd, J=10.1, 4.8 Hz, 1H), 2.63-2.52 (m, 1H); 13C NMR (125 MHz, DMSO) δ ppm 180.06, 168.14, 150.75 (dd, JCF=244.6, 13.2 Hz), 147.93 (dd, JCF=247.5, 13.5 Hz), 144.15, 133.46, 132.55, 131.90 (d, JCF=6.4 Hz), 129.04, 128.86, 128.67, 128.28, 127.43, 124.41, 124.25, 116.12 (d, JCF=17.0 Hz), 86.27, 79.75, 75.03, 68.04, 64.63, 58.16, 53.35.

後処理

  1. temperaturewhile maintaining temperature below 5° C
  2. waitAfter 1.5 h
  3. customThe organic phase was isolated
  4. washsuccessively washed with saturated aq. NaHCO3 (130 mL) and 18% aq
  5. extractionThe combined aqueous phases were extracted with EtOAc (66 mL) and CH2Cl2 (30 mL)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-6c2cbf61fc6a4394bffa87b144fe06eb
出典データセット
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09175013B2

反応ノート

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