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

HRID 351397
Notes
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Reaction equation

HRID 351397 reaction equation
[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]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 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

Product 1

HCID 69287391
5-([1S,2R,4R]-2-benzenesulfonylmethyl-4-tert-butoxycarbonyl-aminocyclohexylamino)-3-(3-trifluoromethylphenyl)pent-2-enoic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-90151e986c1e4ced813233d91c8d90a8
Source dataset
uspto-grants-2007_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07183270B2

Reaction notes

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