Hydrochloric Acid → HCID 71164600, compound

HRID 1182282Notes

Reaction equation

HRID 1182282 reaction equation
[OH:1][C@@H:2]([CH2:13][NH:14][S:15]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1)(=[O:17])=[O:16])[C@@H:3]([NH:5]C(=O)OC(C)(C)C)[CH3:4].O[C@H](CNS(C1C=CC=CN=1)(=O)=O)[C@@H](NC(=O)OC(C)(C)C)C.Cl.[C:48](=[O:81])(OC1C=CC([N+]([O-])=O)=CC=1)[O:49][C@H:50]([CH2:55][N:56]1[CH:60]=[CH:59][C:58]([C:61]2[CH:66]=[CH:65][C:64]([C:67]([F:70])([F:69])[F:68])=[CH:63][CH:62]=2)=[N:57]1)[C:51]([CH3:54])([CH3:53])[CH3:52].C(N(C(C)C)CC)(C)C.C(=O)(O)[O-].[Na+]>O1CCOCC1.C(OCC)C>[OH:1][C@@H:2]([CH2:13][NH:14][S:15]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1)(=[O:17])=[O:16])[C@@H:3]([NH:5][C:48](=[O:81])[O:49][C@H:50]([CH2:55][N:56]1[CH:60]=[CH:59][C:58]([C:61]2[CH:66]=[CH:65][C:64]([C:67]([F:70])([F:68])[F:69])=[CH:63][CH:62]=2)=[N:57]1)[C:51]([CH3:53])([CH3:54])[CH3:52])[CH3:4]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 58981690HCID 58981690, compoundHCID 58981727HCID 58981727, compoundHCID 69512678HCID 69512678, compound

Product 1

HCID 71164600HCID 71164600, compoundYield 81.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 0.101 g (0.29 mmol) of tert-butyl (1S,2S)-2-hydroxy-1-methyl-3-[(2-pyridinylsulfonyl)amino]propylcarbamate & tert-butyl (1S,2R)-2-hydroxy-1-methyl-3-[(2-pyridinylsulfonyl)amino]propylcarbamate in 2 mL of dioxane was added 2.0 mL of a 4.0 M solution of hydrochloric acid in dioxane. The reaction mixture was stirred for 30 min, and then concentrated. This residue was dissolved in 3.0 mL of dimethylformamide and this solution was added to 0.14 g (0.29 mmol) of (1S)-2,2-dimethyl-1-({3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}methyl)propyl 4-(nitro)phenyl carbonate and 1.5 mL (0.87 mmol) of diisopropylethylamine. The reaction mixture was stirred at room temperature for 16 h. A saturated solution of sodium bicarbonate was then added, followed by diethyl ether. The layers were separated, and the organic layer was dried over anhydrous magnesium sulfate, and concentrated under vacuum to afford the crude product. This crude product was purified via silica gel chromatography eluting with ethyl acetate:hexane (1:1) to afford 0.138 g (81%) of (1S)-2,2-dimethyl-1-({3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}methyl)propyl (1S,2S)-2-hydroxy-1-methyl-3-[(2-pyridinylsulfonyl)amino]propylcarbamate & (1S)-2,2-dimethyl-1-({3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}methyl)propyl (1S,2R)-2-hydroxy-1-methyl-3-[(2-pyridinylsulfonyl)amino]propylcarbamate as a colorless oil. 1H-NMR (300 MHz, CDCl3): δ 8.64 (m, 1H), 7.98–7.88 (m, 5H), 7.64–7.47 (m, 4H), 6.60 (s, 1H), 5.01–4.81 (m, 3H), 4.46, 4.42 (2s br, 1H), 4.25–4.17 (m, 2H), 3.59–3.44 (m, 2H), 3.14 (m, 1H), 1.00 (m, 12H); LC-MS 584 (M+H).

Workup

  1. concentrationconcentrated
  2. dissolutionThis residue was dissolved in 3.0 mL of dimethylformamide
  3. stirringThe reaction mixture was stirred at room temperature for 16 h
  4. customThe layers were separated
  5. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  6. concentrationconcentrated under vacuum
  7. customto afford the crude product
  8. customThis crude product was purified via silica gel chromatography
  9. washeluting with ethyl acetate:hexane (1:1)

Sources & evidence

ORD record
ord-7aa075f24e664db29e6fea9e9f3e6c01
Source dataset
uspto-grants-2007_10
Patent number
US07288541B2

Reaction notes

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