Benzyl Alcohol → 3-Benzyloxycarbonylamino-1-(4-methoxy-benzenesulfonyl)-2,3,4,7-tetrahydro-1H-azepine-2-carboxylic acid tert-butyl ester

HRID 1793830Notes

Reaction equation

HRID 1793830 reaction equation
[C:1]([O:5][C:6]([CH:8]1[CH:14](C(O)=O)[CH2:13][CH:12]=[CH:11][CH2:10][N:9]1[S:18]([C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1)(=[O:20])=[O:19])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:32]([CH2:36]CC)CCC)CC.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:46])C=CC=CC=1.[CH2:56]([OH:63])[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1>O1CCOCC1.C(OC(=O)C)C>[C:1]([O:5][C:6]([CH:8]1[CH:14]([NH:32][C:36]([O:63][CH2:56][C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)=[O:46])[CH2:13][CH:12]=[CH:11][CH2:10][N:9]1[S:18]([C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1)(=[O:19])=[O:20])=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 7616TripropylamineHCID 199401P,P-Diphenylphosphinic azideHCID 155505231-(4-Methoxy-benzenesulfonyl)-2,3,4,7-tetrahydro-1H-azepine-2,3-dicarboxylic acid 2-tert-butyl ester

Product 1

HCID 155505263-Benzyloxycarbonylamino-1-(4-methoxy-benzenesulfonyl)-2,3,4,7-tetrahydro-1H-azepine-2-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

The reaction is performed under an Argon athmosphere. 1-(4-Methoxy-benzenesulfonyl)-2,3,4,7-tetrahydro-1H-azepine-2,3-dicarboxylic acid 2-tert-butyl ester (300 mg, 0.73 mmol) is dissolved in 4 ml Dioxane (dry). Tripropylamine (TPA) (98 μl, 0.73 mmol) is added and the reaction is stirred for 15 minutes at RT. Diphenyl phosphoryl azide (157 μl, 0.73 mmol) is added and the reaction is gradually heated to 60° C. for 3 h. The reaction is then allowed to cool to room temperature. Benzyl alcohol (235 μl, 2.2 mmol) is added and the reaction solution is heated to 60° C. over night. The reaction solution is diluted with Ethylacetate and washed with 2 M Citric Acid and Water. The organic phase is separated, dried with MgSO4 and filtrated. The solvent is evaporated and the remaining oil is purified by flash-chromatography, Hexane/Ethylacetate (2:1): Cal. 516.6, found (M)+ 517.

Workup

  1. temperaturethe reaction is gradually heated to 60° C. for 3 h
  2. temperatureto cool to room temperature
  3. temperaturethe reaction solution is heated to 60° C. over night
  4. washwashed with 2 M Citric Acid and Water
  5. customThe organic phase is separated
  6. dry with materialdried with MgSO4
  7. filtrationfiltrated
  8. customThe solvent is evaporated
  9. customthe remaining oil is purified by flash-chromatography, Hexane/Ethylacetate (2:1)

Sources & evidence

ORD record
ord-7439afe6d5fb4e2a838237e99c241613
Source dataset
uspto-grants-2006_04
Patent number
US07022690B2

Reaction notes

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