Acetonitrile → HCID 69224057, compound

HRID 29179Notes

Reaction equation

HRID 29179 reaction equation
[CH2:1]([C@H:8]([NH:31][C:32](=[O:38])[O:33][C:34](C)([CH3:36])[CH3:35])[C@@H:9]([OH:30])[CH:10]([NH:18][S:19]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=1)(=[O:21])=[O:20])[O:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:39](=O)([O:47]C1C=CC([N+]([O-])=O)=CC=1)[O:40]C1COCOC1.C(N(C(C)C)CC)(C)C.C(#N)C>FC(F)(F)C(O)=O>[CH2:1]([C@H:8]([NH:31][C:32](=[O:38])[O:33][CH:34]1[CH2:35][O:47][CH2:39][O:40][CH2:36]1)[C@@H:9]([OH:30])[CH:10]([NH:18][S:19]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=1)(=[O:20])=[O:21])[O:11][CH:12]1[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 81531DiisopropylethylamineHCID 154296011,3-Dioxan-5-yl 4-nitrophenyl carbonateHCID 69223512tert-butyl N-((1S,2R)-1-benzyl-3-(cyclohexyloxy)((4-methoxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate

Product 1

HCID 69224057HCID 69224057, compoundYield 19.2%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

tert-butyl N-((1S,2R)-1-benzyl-3-(cyclohexyloxy)[(4-methoxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate (0.09 mmol, 50 mg) was stirred in 1 mL trifluoroacetic acid (TFA) at room temperature for 5 hours. The TFA was removed under vacuum, and the resulting residue was dissolved in ethyl acetate, washed with 5% aq. potassium carbonate solution, brine, dried over magnesium sulfate, and concentrated to a residue. The resulting free amine, 1,3-dioxan-5-yl 4-nitrophenyl carbonate (0.09 mmol, 25 mg), diisopropylethylamine (0.14 mmol, 0.024 mL), a crystal of N,N-dimethylaminopyridine, 4 Å molecular sieves and acetonitrile (0.5 mL) were combined and stirred at room temperature for 20 hours. The reaction solution was concentrated to a residue, dissolved in ethyl acetate, washed with 1N HCl, 5% aq. potassium carbonate solution, brine, dried over magnesium sulfate, and concentrated under vacuum. The crude residue was purified by silica gel chromatography (2:1 hexanes/ethyl acetate) and crystallization from ether and hexanes to yield 10 mg (19%) of white solid. Rf=0.2 (2:1 hexanes/ethyl acetate); H1-NMR (CDCl3): δ 7.69 (2H,d), 7.29-7.18 (6H,m), 6.96 (2H,d), 5.01-4.93 (1H, m), 4.93-4.85 (1H,m), 4.74-4.70 (1H,m), 4.51-4.45 (1H,m), 4.22-4.11 (1H,m), 3.95-3.72 (7H,m), 3.86 (3H,s), 3.00-2.80 (3H,m), 2.10-1.97 (2H,m), 1.79-1.67 (2H,m), 1.61-1.53(2H,m), 1.38-1.02 (6H,m); MS (ESI): M+H=580.

Workup

  1. customThe TFA was removed under vacuum
  2. dissolutionthe resulting residue was dissolved in ethyl acetate
  3. washwashed with 5% aq. potassium carbonate solution, brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated to a residue
  6. concentrationThe reaction solution was concentrated to a residue
  7. dissolutiondissolved in ethyl acetate
  8. washwashed with 1N HCl, 5% aq. potassium carbonate solution, brine
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated under vacuum
  11. customThe crude residue was purified by silica gel chromatography (2:1 hexanes/ethyl acetate) and crystallization from ether and hexanes

Sources & evidence

ORD record
ord-d8d24b9034444c8eafc38c6ad02a47dd
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Reaction notes

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