Acetic Acid → HCID 135974971, compound

HRID 2075754Notes

Reaction equation

HRID 2075754 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[C:9]1[C:13]([C:14]#[C:15][C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23]([CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][N:26]3[C:31](=[O:41])[C@@H:32]([NH2:40])[CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[O:24])=[CH:18][CH:17]=2)=[CH:12][N:11]([CH3:42])[N:10]=1.C(N(CC)CC)C.[CH:50]1([CH2:55][C:56](O)=[O:57])[CH2:54][CH2:53][CH2:52][CH2:51]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.O.[OH-].[Li+].C(O)(=O)C>ClCCl.O.C(OCC)(=O)C>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[C:9]1[C:13]([C:14]#[C:15][C:16]2[CH:17]=[CH:18][C:19]([NH:22][C:23]([CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][N:26]3[C:31](=[O:41])[C@@H:32]([NH:40][C:56](=[O:57])[CH2:55][CH:50]3[CH2:54][CH2:53][CH2:52][CH2:51]3)[CH2:33][C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)=[O:24])=[CH:20][CH:21]=2)=[CH:12][N:11]([CH3:42])[N:10]=1

Participants

10

Reactant 6

HCID 176Acetic AcidHCID 8471TriethylamineHCID 71606Cyclopentylacetic acidHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 168937Lithium hydroxide, monohydrateHCID 135975028HCID 135975028, compound

Product 1

HCID 135974971HCID 135974971, compoundYield 65.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of compound 19 (6.5 g, 11.57 mmol) in dry dichloromethane (100 mL) was added triethylamine (9.68 mL, 69.42 mmol) and cyclopentylacetic acid (4.35 mL, 34.71 mmol). The resultant solution was stirred at rt for 5 min. (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP, 15.36 g, 34.71 mmol) was added into the above solution in portions. The final mixture was stirred at rt overnight. The solvent was removed with rotavapor. To the residua was added THF (60 mL) and methanol (60 mL). A suspension of lithium hydroxide monohydrate (5.0 g, 119.2 mmol) in water (30 mL) was slowly added to the above solution. The mixture was stirred at rt for 1.5 hours and then neutralized with acetic acid (7.0 mL, 122.3 mmol). The mixture was diluted with ethyl acetate (˜300 mL), and washed with brine, and dried over sodium sulfate. It was filtered, concentrated and purified with silica column chromatography eluting with dichloromethane-ethyl acetate (v/v 9/1). After crystallizing with hexanes/ethyl acetate, the title compound (20, 5.1 g) was obtained as white solid in 65.6% yield.

Workup

  1. additionwas added into the above solution in portions
  2. customThe solvent was removed with rotavapor
  3. additionTo the residua was added THF (60 mL) and methanol (60 mL)
  4. additionwas slowly added to the above solution
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationIt was filtered
  8. concentrationconcentrated
  9. custompurified with silica column chromatography
  10. washeluting with dichloromethane-ethyl acetate (v/v 9/1)
  11. customAfter crystallizing with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-b049c980de5144b7aa7b4639d7a35727
Source dataset
uspto-grants-2011_04
Patent number
US07923004B2

Reaction notes

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