Acetic Acid → HCID 69039943, compound

HRID 351382Notes

Reaction equation

HRID 351382 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([N:8]2[CH2:12][CH2:11][C@H:10]([CH2:13][C:14]3([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=4)[O:18][CH2:17][CH2:16][O:15]3)[C:9]2=[O:29])[C@H:4]([CH2:30][S:31]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)(=[O:33])=[O:32])[CH2:3]1.[C:40](O)(=O)[CH3:41].[C:44](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.CCOC(C)=O.CC(C)=O>[CH:40]([NH:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([N:8]2[CH2:12][CH2:11][C@H:10]([CH2:13][C:14]3([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:26])([F:27])[F:28])[CH:20]=4)[O:15][CH2:16][CH2:17][O:18]3)[C:9]2=[O:29])[C@H:4]([CH2:30][S:31]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)(=[O:32])=[O:33])[CH2:3]1)([CH3:41])[CH3:44]

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 69035635HCID 69035635, compound

Product 1

HCID 69039943HCID 69039943, compoundYield 58%

Reagents, catalysts & solvents 3

HCID 180AcetoneCatalystHCID 63651,1-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 39h-b (170 mg, 300 μmol), acetone (871 μL, 11.9 μmol), acetic acid (69.1 μL, 1.20 mmol), and sodium triacetoxyborohydride (255 mg, 1.20 mmol) in dichloroethane (17 mL) was stirred at room temperature for 2 h. The reaction was diluted with EtOAc (500 mL), washed with saturated NaHCO3 (3×150 mL), water (2×100 mL), and brine (150 mL), dried over Na2SO4, filtered, and evaporated. The residue was purified by CombiFlash chromatography (silica, 0–10% MeOH/CH2Cl2) to provide (R*)-1-((1S*,2R*,4R*)-4-(isopropylamino)-2-(phenylsulfonylmethyl)cyclohexyl)-3-((2-(3-(trifluoromethyl)phenyl)-1,3-dioxolan-2-yl)methyl)pyrrolidin-2-one (39i-b, 106 mg, 58%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.89 (d, J=7.2 Hz, 2H), 7.68 (s, 1H), 7.64–7.39 (m, 6H), 4.20 (s, 1H), 4.05–3.90 (m, 2H), 3.81–3.60 (m, 3H), 3.48–3.11 (m, 4H), 3.10–2.88 (m, 1H), 2.60–2.10 (m, 5H), 2.09–1.60 (m, 8H), 1.43–1.00 (m, 6H); 19F NMR (282 MHz, CDCl3) δ −62.9; ESI MS m/z 609 [C31H39F3N2O5S+H]+.

Workup

  1. washwashed with saturated NaHCO3 (3×150 mL), water (2×100 mL), and brine (150 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by CombiFlash chromatography (silica, 0–10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-74b177bc21464446914e0f523caf6601
Source dataset
uspto-grants-2007_02
Patent number
US07183270B2

Reaction notes

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