Sodium hydride → 5-([1S,2R,4R]-2-benzenesulfonylmethyl-4-tert-butoxycarbonyl-aminocyclohexylamino)-3-(3-trifluoromethylphenyl)pent-2-enoic acid tert-butyl ester

HRID 351397

반응식

HRID 351397 반응식
[H-].[Na+].[C:3]([O:7][C:8](=[O:16])[CH2:9]P(OC)(OC)=O)([CH3:6])([CH3:5])[CH3:4].C(OC(=O)N[C@@H]1[CH2:29][CH2:28][C@H:27]([NH:30][CH2:31][CH2:32][C:33](=O)[C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[CH:35]=2)[C@H:26]([CH2:45][S:46]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)(=[O:48])=[O:47])[CH2:25]1)(C)(C)C.[Cl-].[NH4+:57]>O1CCCC1>[C:3]([O:7][C:8](=[O:16])[CH:9]=[C:33]([C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:41])([F:43])[F:42])[CH:35]=1)[CH2:32][CH2:31][N:30]([NH2:57])[C@H:27]1[CH2:28][CH2:29][C@@H:9]([C:8]([O:7][C:3]([CH3:4])([CH3:5])[CH3:6])=[O:16])[CH2:25][C@H:26]1[CH2:45][S:46]([C:49]1[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=1)(=[O:47])=[O:48])([CH3:6])([CH3:5])[CH3:4]

참가 물질

6

반응물 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 4564495tert-Butyl DimethylphosphonoacetateHCID 69037372(1R,3R,4S)-{3-benzenesulfonylmethyl-4-[3-oxo-3-(3-trifluoromethylphenyl)-propylamino]cyclohexyl}carbamic acid tert-butyl ester

생성물 1

HCID 692873915-([1S,2R,4R]-2-benzenesulfonylmethyl-4-tert-butoxycarbonyl-aminocyclohexylamino)-3-(3-trifluoromethylphenyl)pent-2-enoic acid tert-butyl ester

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A suspension of sodium hydride (60%, 176 mg, 4.4 mmol) in tetrahydrofuran (5 mL) was stirred on an ice bath and treated dropwise over 5 min with dimethylphosphonoacetic acid tert-butyl ester (0.79 mL, 4.0 mmol). The mixture was stirred at room temperature for 25 min, then was cooled on an ice bath and treated with a solution of (1R,3R,4S)-{3-benzenesulfonylmethyl-4-[3-oxo-3-(3-trifluoromethylphenyl)-propylamino]cyclohexyl}carbamic acid tert-butyl ester (1.138 g, 2.0 mmol) in tetrahydrofuran (5 mL). The mixture was stirred at room temperature for 2.5 h, then was treated with saturated aqueous ammonium chloride. The mixture was extracted with ethyl acetate, and the organic extracts were dried over sodium sulfate and concentrated under vacuum. The residue was purified by flash column chromatography, eluting with 25% ethyl acetate-hexane, to provide the E isomer of 5-([1S,2R,4R]-2-benzenesulfonylmethyl-4-tert-butoxycarbonyl-aminocyclohexylamino)-3-(3-trifluoromethylphenyl)pent-2-enoic acid tert-butyl ester (511 mg) as a white solid. MS found: (M+H)+=667.41. Further elution with 40% ethyl acetate-hexane provided the corresponding Z isomer (567 mg) as a white glassy solid. MS found: (M+H)+=667.41.

후처리

  1. stirringThe mixture was stirred at room temperature for 25 min
  2. temperaturewas cooled on an ice bath
  3. stirringThe mixture was stirred at room temperature for 2.5 h
  4. extractionThe mixture was extracted with ethyl acetate
  5. dry with materialthe organic extracts were dried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by flash column chromatography
  8. washeluting with 25% ethyl acetate-hexane

출처 및 근거

ORD 기록
ord-90151e986c1e4ced813233d91c8d90a8
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07183270B2

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