Trifluoroacetic acid → HCID 69223259, compound

HRID 29170Notes

Reaction equation

HRID 29170 reaction equation
[NH2:1][C@@H:2]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C@H:3]([OH:23])[CH2:4][N:5](OC1CCCC1)[S:6]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)(=[O:8])=[O:7].F[C:32](F)(F)[C:33]([OH:35])=O.[CH2:38]([O:45][C:46](Cl)=[O:47])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.[CH:49](N(CC)C(C)C)([CH3:51])[CH3:50]>ClCCl>[CH2:24]([C@H:2]([NH:1][C:46](=[O:47])[O:45][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C@@H:3]([OH:23])[CH:4]([NH:5][S:6]([C:9]1[CH:10]=[CH:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=1)(=[O:8])=[O:7])[O:35][CH:33]1[CH2:32][CH2:51][CH2:49][CH2:50]1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 57010648N1-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N1-(cyclopentyloxy)-4-methoxy-1-benzenesulfonamide

Product 1

HCID 69223259HCID 69223259, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N1-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N1-(cyclopentyloxy)-4-methoxy-1-benzenesulfonamide×trifluoracetic acid (Step 1, Example 48), (50 mg, 0.091 mmol) in approximately 1.5 mL of dichloromethane under Argon was added benzylchloroformate (15.6 μL, 0.109 mmol) followed by N,N-diisopropylethylamine (47.9 μL, 0.273 mmol). After stirring 18 hours, the reaction mixture was evaporated in vacuo to a residue and purified on a preparative silica gel TLC plate (20×20 cm, 1000 μM) eluting with 95:5 methylene chloride:methanol. The product band was removed, eluted with 4:1 methylene chloride:methanol, filtered, and evaporated in vacuo. The residue was partitioned between dichloromethane and water. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was lyophilized from acetonitrile and water to provide phenylmethyl N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)[(4-methoxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate (37 mg, 71%). H1-NMR (methanol-D4) 1.71 (m, 8H), 2.59 (m, 1H), 2.93 (m, 2H), 3.10 (m, 1H), 3.81 (m, 2H), 3.83 (s, 3H), 4.86 (m, 3H), 7.06 (m, 2H), 7.21 (m, 10H), 7.73 (m, 2H). MS(ESI): 591 (M+Na).

Workup

  1. customthe reaction mixture was evaporated in vacuo to a residue
  2. custompurified on a preparative silica gel TLC plate (20×20 cm, 1000 μM)
  3. washeluting with 95:5 methylene chloride
  4. customThe product band was removed
  5. washeluted with 4:1 methylene chloride
  6. filtrationmethanol, filtered
  7. customevaporated in vacuo
  8. customThe residue was partitioned between dichloromethane and water
  9. customThe organic layer was separated
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. customevaporated in vacuo

Sources & evidence

ORD record
ord-9450d50a0257487ab0b76db14c5bbf0c
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Reaction notes

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