Formaldehyde → HCID 86618148, compound

HRID 2246576Notes

Reaction equation

HRID 2246576 reaction equation
[C:1]([NH:4][C@@H:5]1[CH2:10][C@H:9]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[CH2:8][CH2:7][C@@H:6]1[N:21]1[CH2:25][CH2:24][C@H:23]([NH:26][C:27](=[O:36])[O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:22]1=[O:37])(=[O:3])[CH3:2].[CH2:38](N(CC)CC)C.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[C:1]([NH:4][C@@H:5]1[CH2:10][C@H:9]([N:11]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)[CH3:38])[CH2:8][CH2:7][C@@H:6]1[N:21]1[CH2:25][CH2:24][C@H:23]([NH:26][C:27](=[O:36])[O:28][CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:22]1=[O:37])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 86618147HCID 86618147, compound

Product 1

HCID 86618148HCID 86618148, compoundYield 97.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A sample of benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-(4-methoxybenzylamino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (54.45 g, 107 mmol) was dissolved in dichloromethane (400 mL). The resultant solution was cooled to 0° C. under N2 stream and then charged sequentially with triethylamine (29.8 mL, 214 mmol), aqueous formaldehyde (11.96 mL of a 37% solution, 161 mmol), and sodium triacetoxyborohydride (34.0 g, 161 mmol). The ice bath was removed and the reaction was stirred at RT for 2 h before being diluted with 750 mL EtOAc and washed with sat. NaHCO3 (2×250 mL). The organic phase was concentrated in vacuo and the resultant residue was dissolved in EtOAc (750 mL). The organic phase was washed with acid [2×(200 mL 1N HCl/300 mL H2O)]. The acidic washes were combined and then basified with 6N NaOH (80 mL) and sat. NaHCO3 (70 mL). The mixture was extracted with EtOAc (3×500 mL). The organic extracts were combined, washed with brine (1×100 mL), dried (MgSO4), filtered, and concentrated in vacuo. The residue was dissolved in methylene chloride and concentrated; this was repeated twice to afford benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-((4-methoxybenzyl)(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate (54.14 g, 104 mmol, 97% yield) as a hard white microcrystalline foam after pumping on high vacuum. LC/MS found [M+H]+=523.6.

Workup

  1. customThe ice bath was removed
  2. additionbefore being diluted with 750 mL EtOAc
  3. washwashed with sat. NaHCO3 (2×250 mL)
  4. concentrationThe organic phase was concentrated in vacuo
  5. dissolutionthe resultant residue was dissolved in EtOAc (750 mL)
  6. washThe organic phase was washed with acid [2×(200 mL 1N HCl/300 mL H2O)]
  7. extractionThe mixture was extracted with EtOAc (3×500 mL)
  8. washwashed with brine (1×100 mL)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. dissolutionThe residue was dissolved in methylene chloride
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-30c0011236a1419c8ee742cf5008676e
Source dataset
uspto-grants-2010_03
Patent number
US07687508B2

Reaction notes

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