Sodium Fluoride → HCID 46841478, compound

HRID 220741Notes

Reaction equation

HRID 220741 reaction equation
[C:1]([N:8]1[CH2:12][C@@H:11]([F:13])[CH2:10][C@H:9]1[C:14]([OH:16])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[F-].[Na+].[F:19]C1(F)N(C)CCN1C>ClCCl>[C:1]([N:8]1[CH2:12][C@@H:11]([F:13])[CH2:10][C@H:9]1[C:14]([F:19])=[O:16])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

5

Reactant 3

HCID 5235Sodium FluorideHCID 2756017(4S)-1-tert-Butoxycarbonyl-4-fluoro-L-prolineHCID 27791112,2-Difluoro-1,3-dimethylimidazolidine

Product 1

HCID 46841478HCID 46841478, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

(2S,4S)—N-Boc-4-fluoropyrrolidine-2-carboxylic acid (1.17 g, 5 mmol) and sodium fluoride (0.63 g, 15 mmol) were put in a fluoropolymer (PFA) vessel, and 10 ml of dichloromethane was added into the vessel. The mixture was cooled with ice. A solution of 2,2-difluoro-1,3-dimethylimidazolidine (817 mg, 6 mmol) in 2 ml of dichloromethane was added slowly. After 5 minutes of addition, the ice bath was removed and the mixture warmed to room temperature. The reaction mixture was stirred for a total 20 min. 19F NMR analysis of the reaction mixture showed that (2S,4S)—N-Boc-4-fluoropyrrolidine-2-carbonyl fluoride (Id) was produced in 85% yield. The mixture was diluted with 10 ml of dichloromethane and washed with water. The organic layer was dried over anhydrous magnesium sulfate and filtered. Removal of solvent followed by washing with a small amount of water and then drying gave 846 mg (yield 72%) of (2S,4S)—N-Boc-4-fluoropyrrolidine-2-carbonyl fluoride (Id): Oil: 19F-NMR (CDCl3) (as a 6:4 mixture of two rotamers) δ 28.22 (s, 0.6 F, COF), 28.14 (s, 0.4 F, COF), −173.18 (m, 1 F, CF): 1H-NMR (CDCl3) 8 (as a mixture of two rotamers) 1.40 (s, 0.55×9H, t-Bu), 1.43 (s, 0.45×9H, t-Bu), 2.2-2.6 (m, 2H), 3.45-3.95 (m, 2H), 4.5-4.7 (m, 1H), 5.22 (br.d, J=51.9 Hz, 1H, CHF): 13C-NMR (CDCl3) 8 (as a mixture of two rotamers); 90.94 (d, J=177.0 Hz, 1H, CF), 92.02 (d, J=177.0 Hz, CF), 153.06 (s, CON), 153.82 (s, CON), 161.50 (d, J=372.1 Hz, COF), 161.66 (d, J=372.8 Hz, COF): High Resolution Mass/ESI-APCI method (solvent; methanol); (M-F+OCH3+Na)+ 270.1109 [calcd 270.1112 for (C11H18FNO4+Na)].

Workup

  1. temperatureThe mixture was cooled with ice
  2. additionAfter 5 minutes of addition
  3. customthe ice bath was removed
  4. customwas produced in 85% yield
  5. washwashed with water
  6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customRemoval of solvent
  9. washby washing with a small amount of water
  10. customdrying

Sources & evidence

ORD record
ord-dc6a63136e494902a30afe50732554ba
Source dataset
uspto-grants-2012_06
Patent number
US08203003B2

Reaction notes

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