Isopropanol → Diethylamine

HRID 1400073ノート

反応式

HRID 1400073 の反応式
[NH2:1][CH:2]1[CH2:9][C:8]2([C:10]([N:12]3[C@H:17]4[CH2:18][CH2:19][C@H:13]3[CH2:14][N:15]([C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][N:21]=3)[CH2:16]4)=[O:11])[CH:4]([CH2:5][CH2:6][CH2:7]2)[CH2:3]1.C(N(CCCC)CCCC)CCC.C(O)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH3:61][O:62][C@H:63]1[C:68](=O)[CH2:67][CH2:66][O:65][CH2:64]1>C(OC(C)C)(=O)C.ClCCl>[CH2:10]([NH:12][CH2:13][CH3:14])[CH3:8].[CH3:61][O:62][C@@H:63]1[CH2:64][O:65][CH2:66][CH2:67][C@@H:68]1[NH:1][C@H:2]1[CH2:9][C@@:8]2([C:10]([N:12]3[C@H:13]4[CH2:19][CH2:18][C@@H:17]3[CH2:16][N:15]([C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][N:21]=3)[CH2:14]4)=[O:11])[C@H:4]([CH2:5][CH2:6][CH2:7]2)[CH2:3]1

参加物

9

反応物 5

HCID 3776IsopropanolHCID 7622TributylamineHCID 5049666Sodium triacetoxyborohydrideHCID 11320949(R)-3-methoxydihydro-2H-pyran-4(3H)-oneHCID 89823484(2-aminooctahydropentalen-3a-yl)((1S,5S)-3-(4-(trifluoromethyl)pyridin-2-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone

生成物 2

HCID 8021Diethylamine収率 0.1%HCID 898234821,5-anhydro-2,3-dideoxy-4-O-methyl-3-{[(2R,3aR,6aR)-3a-({(1R,5S)-3-[4-(trifluoromethyl)pyridin-2-yl]-3,8-diazabicyclo[3.2.1]oct-8-yl}carbonyl)octahydropentalen-2-yl]amino}-D-erythro-pentitol

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 7915Isopropyl Acetate溶媒

実験手順

A solution of Example 8C (50 mg, 0.12 mmol) in isopropyl acetate (5 mL) was cooled with an ice bath. Tributyl amine (11 mg, 0.06 mmol) followed by addition of isopropyl alcohol (16.8 mg, 0.28 mmol) was added to the solution. Sodium triacetoxyborohydride (59 mg, 0.28 mmol) was added at 5° C. After stirring for 1 hour, a solution of Example 1I (23.4 mg, 0.18 mmol) in dichloromethane was added to the reaction mixture. Then the mixture was stirred at room temperature overnight. The reaction mixture was quenched with saturated sodium bicarbonate and extracted with ethyl acetate. The combined organic fractions were washed with brine, dried in vacuo and concentrated to provide a diastereomeric mixture. The diastereomeric mixture was separated by chiral SFC (Column: AD 250 mm*30 mm, 5 μm; Mobile phase:A, supercritical CO2; B, isopropyl alcohol with 0.1% diethylamine, A:B=80:20 with a flow rate of 70 mL/min) to afford the title compound (peak 1, retention time: 7.11 minutes) and Example 41 (peak 2, retention time: 7.94 minutes); MS (ESI) m/z 523 (M+H)+.

後処理

  1. additionwas added to the solution
  2. stirringThen the mixture was stirred at room temperature overnight
  3. customThe reaction mixture was quenched with saturated sodium bicarbonate
  4. extractionextracted with ethyl acetate
  5. washThe combined organic fractions were washed with brine
  6. customdried in vacuo
  7. concentrationconcentrated
  8. customto provide a diastereomeric mixture
  9. customThe diastereomeric mixture was separated by chiral SFC (Column

出典と根拠

ORDレコード
ord-f7a5b7c362c64e8d8421b0abe47224ae
出典データセット
uspto-grants-2014_12
特許番号
US08906911B2

反応ノート

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