Acetic Acid → HCID 86702367, compound

HRID 1894176Notes

Reaction equation

HRID 1894176 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)[C:5]([NH2:17])=[CH:4][N:3]=1.[C:18]([O:22][C:23]([N:25]1[CH2:29][C@H:28]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[CH2:27][C@H:26]1[CH:38]=O)=[O:24])([CH3:21])([CH3:20])[CH3:19].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[C:18]([O:22][C:23]([N:25]1[CH2:29][C@H:28]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:32])[CH3:33])[CH2:27][C@H:26]1[CH2:38][NH:17][C:5]1[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)=[N:7][C:2]([Cl:1])=[N:3][CH:4]=1)=[O:24])([CH3:21])([CH3:20])[CH3:19]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 10969557tert-Butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylateHCID 58243054HCID 58243054, compound

Product 1

HCID 86702367HCID 86702367, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of Compound 1c (191 mg, 0.759 mmol) in 1,2-dichloroethane (4 mL) was added Compound 27d (250 mg; 0.759 mmol) and acetic acid (0.2 mL) at ambient temperature, and the mixture was stirred at room temperature for 1.5 h. The mixture was then treated with NaB(OAc)3H (240 mg; 1.14 mmol) and continually stirred at room temperature for 4 h. The resultant mixture was diluted with CH2Cl2, then washed with saturated NaHCO3 (aq) and water. The organic phase was washed sequentially with water and brine, and then dried over Na2SO4. The mixture was filtered and the filtrate was evaporated under reduced pressure to give the crude material. The crude material was purified by flash column chromatography (SiO2), eluting with a heptane-EtOAc gradient to afford Compound 27e. 1H-NMR (400 MHz, CDCl3): δ 7.70-7.75 (m, 1H), 7.10-7.13 (m, 2H), 6.94-7.01 (m, 2H), 5.79 (br. s, 0.6H), 4.73 (br. s, 0.4H), 4.30-4.39 (m, 2H), 3.84 (s, 3H), 3.12-3.69 (m, 4H), 2.06-2.16 (m, 1H), 1.80-1.87 (m, 1H), 1.45-1.48 (m, 9H), 0.88 (s, 9H), 0.08 (s, 6H); MS: m/z 565.2 (M+H)+.

Workup

  1. stirringcontinually stirred at room temperature for 4 h
  2. washwashed with saturated NaHCO3 (aq) and water
  3. washThe organic phase was washed sequentially with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationThe mixture was filtered
  6. customthe filtrate was evaporated under reduced pressure
  7. customto give the crude material
  8. customThe crude material was purified by flash column chromatography (SiO2)
  9. washeluting with a heptane-EtOAc gradient

Sources & evidence

ORD record
ord-7528801acbf0449aa3f2220d5fd1c83b
Source dataset
uspto-grants-2013_08
Patent number
US08513271B2

Reaction notes

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