Isopropanol → Diethylamine

HRID 1400073노트

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HRID 1400073 반응식
[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

참가 물질

9

반응물 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

생성물 2

HCID 8021Diethylamine수율 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

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 7915Isopropyl Acetate용매

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-f7a5b7c362c64e8d8421b0abe47224ae
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08906911B2

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