Formaldehyde → N,N-dimethyl--O--(9-phenyl-9H-fluoren-9-yl)-L-serine methyl ester

HRID 1275786Notes

Reaction equation

HRID 1275786 reaction equation
[CH3:1][O:2][C:3](=[O:27])[C@H:4]([CH2:6][O:7][C:8]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:20]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:14]2[C:9]1=[CH:10][CH:11]=[CH:12][CH:13]=2)N.[CH2:28]=O.O.[C:31]([BH3-])#[N:32].[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[CH3:1][O:2][C:3](=[O:27])[C@H:4]([CH2:6][O:7][C:8]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:20]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:14]2[C:9]1=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:32]([CH3:31])[CH3:28]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 15516030O-(9-phenyl-9H-fluoren-9-yl)-L-serine methyl ester

Product 1

HCID 54462480N,N-dimethyl--O--(9-phenyl-9H-fluoren-9-yl)-L-serine methyl esterYield 81.6%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent2×

Procedure

To a stirred solution of 0.57 g (1.6 mmol) O-(9-phenyl-9H-fluoren-9-yl)-L-serine methyl ester (Example 4a, Step 2), 0.150 g (5 mmol) paraformaldehyde and water (0.4 mL) in methanol (5 mL) was added dropwise a solution of 0.11 g (0.8 mmol) zinc chloride and 0.1 g (1.6 mmol) sodium cyanoborohydride in methanol (5 mL) at room temperature. The mixture was stirred at room temperature for 16 h, the solvent was evaporated, water (50 mL) was added and the mixture extracted with dichloromethane (3×20 mL). The combined dichloromethane extracts were washed with brine, dried (MgSO4), the solvent evaporated and the residue chromatographed on silica gel with 30% ethyl acetate in hexanes to give 0.5 g (yield 81.6%) N,N-dimethyl--O--(9-phenyl-9H-fluoren-9-yl)-L-serine methyl ester as an oil. 1H NMR (CDCl3, 300 MHz) δ: 7.68 (d, 2H), 7.40-7.10 (m, 11H), 3.73 (s, 3H), 3.40-3.15 (m, 3H), 2.29 (s, 6H); 13C NMR (CDCl3, 75 MHz) 6: 171.3, 146.6, 146.5, 143.2, 140.7, 140.5, 129.1, 129.0, 128.2, 128.1, 128.0, 127.0, 125.5, 125.4, 125.3, 120.0, 119.9, 88.7, 67.7, 61.9, 51.4, 42.6, 14.2.

Workup

  1. customthe solvent was evaporated
  2. additionwater (50 mL) was added
  3. extractionthe mixture extracted with dichloromethane (3×20 mL)
  4. washThe combined dichloromethane extracts were washed with brine
  5. dry with materialdried (MgSO4)
  6. customthe solvent evaporated
  7. customthe residue chromatographed on silica gel with 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-ab1b534fbd564852a658c96a7d0a7686
Source dataset
uspto-grants-2000_12
Patent number
US06162824

Reaction notes

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