Diisopropylethylamine → tert-butyl (1R,3R,4S)-3-(methoxymethyl)-4-(2-(3-(trifluoromethyl)benzamido)acetamido)cyclohexylcarbamate

HRID 2225246Notes

Reaction equation

HRID 2225246 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@@H:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:4][C@H:3]1[CH2:16][O:17][CH3:18].[F:19][C:20]([F:35])([F:34])[C:21]1[CH:22]=[C:23]([CH:31]=[CH:32][CH:33]=1)[C:24]([NH:26][CH2:27][C:28](O)=[O:29])=[O:25].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(#N)C.C(OCC)(=O)C>[CH3:18][O:17][CH2:16][C@H:3]1[C@@H:2]([NH:1][C:28](=[O:29])[CH2:27][NH:26][C:24](=[O:25])[C:23]2[CH:31]=[CH:32][CH:33]=[C:21]([C:20]([F:19])([F:35])[F:34])[CH:22]=2)[CH2:7][CH2:6][C@@H:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:13])[CH3:14])[CH2:4]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 2777432((3-(Trifluoromethyl)benzoyl)amino)acetic acidHCID 68765639tert-butyl (1R,3R,4S)-4-amino-3-(methoxymethyl)cyclohexylcarbamate

Product 1

HCID 86596947tert-butyl (1R,3R,4S)-3-(methoxymethyl)-4-(2-(3-(trifluoromethyl)benzamido)acetamido)cyclohexylcarbamateYield 60.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of tert-butyl (1R,3R,4S)-4-amino-3-(methoxymethyl)cyclohexylcarbamate (45 mg, assumed 0.163 mmol) in acetonitrile (1.5 mL) was treated sequentially with 2-(3-(trifluoromethyl)benzamido)acetic acid (43 mg, 0.174 mmol, see PCT WO 0250019), diisopropylethylamine (61 μL, 0.348 mmol) and TBTU (62 mg, 0.192 mmol). The mixture was stirred at rt for 2.75 h, then was diluted with ethyl acetate, washed sequentially with 1.0 M aqueous HCl, saturated aqueous NaHCO3, water and brine, dried over Na2SO4 and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel, eluting with 1:3 v/v hexane-ethyl acetate, to provide tert-butyl (1R,3R,4S)-3-(methoxymethyl)-4-(2-(3-(trifluoromethyl)benzamido)acetamido)cyclohexylcarbamate as a white solid (48 mg). MS found: (M+H)+=488.3.

Workup

  1. washwashed sequentially with 1.0 M aqueous HCl, saturated aqueous NaHCO3, water and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified by flash column chromatography on silica gel
  5. washeluting with 1:3 v/v hexane-ethyl acetate

Sources & evidence

ORD record
ord-e4f72adb51064f89bff319026b14b724
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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