Sodium Carbonate → (S)-2-(Tert-butoxycarbonylamino)-3-(3'-chlorobiphenyl-4-yl)propanoic acid

HRID 333334노트

반응식

HRID 333334 반응식
[C:1]([NH:8][C@H:9]([C:18]([OH:20])=[O:19])[CH2:10][C:11]1[CH:16]=[CH:15][C:14](Br)=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[Cl:21][C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:4]([O:3][C:1]([NH:8][C@@H:9]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:26]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:21])[CH:27]=2)=[CH:13][CH:12]=1)[C:18]([OH:20])=[O:19])=[O:2])([CH3:7])([CH3:6])[CH3:5]

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 2734477(2S)-3-(4-bromophenyl)-2-{[(tert-butoxy)carbonyl]amino}propanoic acid

생성물 1

HCID 58280562(S)-2-(Tert-butoxycarbonylamino)-3-(3'-chlorobiphenyl-4-yl)propanoic acid수율 66%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

To a solution of Boc-4-bromo-L-phenylalanine (15 g, 43.6 mmol) in DME (180 ml) at room temperature was added 3-chlorobenzeneboronic acid (8.52 g, 54.5 mmol) followed by aq. Na2CO3 (32.7 ml, 65.4 mmol) and Pd(PPh3)4 (1.511 g, 1.307 mmol). The mixture was stirred at 85° C. for 3 hours. The reaction mixture was filtered and added EtOAc and acidified by 1M HCl to pH˜5. The combined organic layer was washed with brine and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The obtained residue was purified by flash chromatography (silica gel, 5 to 20% EtOAc/Heptane) and gave the title compound: 12.0 g (yield: 66%). LCMS (condition A): 374.2 (M−1); retention time=1.57 min.

후처리

  1. filtrationThe reaction mixture was filtered
  2. additionadded EtOAc
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified by flash chromatography (silica gel, 5 to 20% EtOAc/Heptane)

출처 및 근거

ORD 기록
ord-04d81aa93bf7411a99e92ef80f624111
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877815B2

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