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Methyl 3-formylbenzoate → (S)-3-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-benzoic acid methyl ester

HRID 507109
ノート
印刷プレビュー

反応式

HRID 507109 の反応式
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]=O)[CH:5]=1.[F:13][C:14]([F:50])([F:49])[C:15]1[CH:16]=[C:17]([CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)[CH2:18][N:19]([C:36]1[N:37]=[N:38][N:39]([CH3:41])[N:40]=1)[C@H:20]1[CH2:26][CH2:25][CH2:24][NH:23][C:22]2[CH:27]=[C:28]([C:32]([F:35])([F:34])[F:33])[C:29]([CH3:31])=[CH:30][C:21]1=2.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C.ClCCCl.C(Cl)Cl>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][N:23]2[CH2:24][CH2:25][CH2:26][C@H:20]([N:19]([CH2:18][C:17]3[CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=[C:15]([C:14]([F:13])([F:50])[F:49])[CH:16]=3)[C:36]3[N:37]=[N:38][N:39]([CH3:41])[N:40]=3)[C:21]3[CH:30]=[C:29]([CH3:31])[C:28]([C:32]([F:34])([F:33])[F:35])=[CH:27][C:22]2=3)[CH:5]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 639145Methyl 3-formylbenzoateHCID 5049666Sodium triacetoxyborohydrideHCID 59432408(S)-(3,5-bistrifluoromethylbenzyl)-(2-methyl-2H-tetrazol-5-yl)-(7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)amine

生成物 1

HCID 11563865(S)-3-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-benzoic acid methyl ester
収率 53%

試薬・触媒・溶媒 3

HCID 111,2-Dichloroethane溶媒HCID 176Acetic Acid溶媒HCID 6344Dichloromethane溶媒

実験手順

Add 3-formylbenzoic acid methyl ester (133 mg, 0.815 mmol) to a solution of (S)-(3,5-bis-trifluoromethylbenzyl)-(2-methyl-2H-tetrazol-5-yl)-(7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)amine (Example 3, Step 18) (150 mg, 0.272 mmol) in acetic acid (1 mL) and 1,2-dichloroethane (10 mL) at room temperature under nitrogen and stir for 2 h. Add sodium triacetoxy borohydride (231 mg, 1.08 mmol) and stir for 3 h. Dilute the mixture with methylene chloride (30 mL) and wash with saturated aqueous sodium bicarbonate solution (2×10 mL). Extract the combined aqueous washes with methylene chloride (20 mL) and wash the combined organic extracts with brined (20 mL) and dry over anhydrous sodium sulfate. Remove the solvents under reduced pressure and purify the residue by column chromatography on silica gel, eluting with ethyl acetate/hexanes (1:2), to provide the title compound as a white solid (101 mg, 53%): mp 62-65° C. dec; 1H NMR (CDCl3, 300 MHz) δ 1.50-1.70 (m, 2H), 2.07-2.25 (m, 2H), 2.29 (s, 3H), 2.73-2.85 (m, 1H), 2.95-3.09 (m, 1H), 3.89 (s, 3H), 4.18 (s, 3H), 4.31-4.40 (m, 2H), 4.81-5.02 (m, 2H), 6.93 (s, 1H), 7.31-7.42 (m, 2H), 7.55-7.63 (m, 4H), 7.79-7.82 (m, 1H), 7.89-7.92 (m, 1H), 8.10 (s, 1H); ESI MS m/z 701 [C32H29F9N6O2+H]+; HPLC 97.6%, tR 19.7 min.

後処理

  1. washwash with saturated aqueous sodium bicarbonate solution (2×10 mL)
  2. extractionExtract the combined aqueous washes with methylene chloride (20 mL)
  3. washwash the combined organic extracts with brined (20 mL)
  4. dry with materialdry over anhydrous sodium sulfate
  5. customRemove the solvents under reduced pressure
  6. custompurify the residue by column chromatography on silica gel
  7. washeluting with ethyl acetate/hexanes (1:2)

出典と根拠

ORDレコード
ord-38c4306c07c648729d42f9513591ec5a
出典データセット
uspto-grants-2010_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07786108B2

反応ノート

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