Water → (4R)-tert-butyl 2-(3-fluorophenyl)-4-hydroxypyrrolidine-1-carboxylate

HRID 513005Notes

Reaction equation

HRID 513005 reaction equation
[Si]([O:8][C@H:9]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:11]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=2)[CH2:10]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].O>C1COCC1>[F:27][C:23]1[CH:22]=[C:21]([CH:11]2[CH2:10][C@@H:9]([OH:8])[CH2:13][N:12]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 962WaterHCID 2724141Tetrabutylammonium FluorideHCID 66684243(4R)-tert-butyl 4-(tert-butyldimethylsilyloxy)-2-(3-fluorophenyl)pyrrolidine-1-carboxylate

Product 1

HCID 66684241(4R)-tert-butyl 2-(3-fluorophenyl)-4-hydroxypyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (4R)-tert-butyl 4-(tert-butyldimethylsilyloxy)-2-(3-fluorophenyl)pyrrolidine-1-carboxylate (I-3) (18.1 g, 38.2 mmol) in THF (76 mL) at room temperature was added TBAF (50 mL of a 1.0 M solution in THF, 49.7 mmol). The mixture was stirred at room temperature for 2 hours then poured into water. The mixture was extracted with EtOAc, washed with water and brine, dried over sodium sulfate, filtered and concentrated. The mixture was purified by column chromatography on silica gel with EtOAc/hexanes gradient as eluant to yield (4R)-tert-butyl 2-(3-fluorophenyl)-4-hydroxypyrrolidine-1-carboxylate (1-4). 1H NMR (400 MHz, CDCl3) δ 7.32-7.26 (m, 1 H), 7.07 (bd, J=7.6 Hz, 1 H), 7.01 (bd, J=7.5 Hz, 1 H), 6.92 (dt, J=8.4 Hz, 1 H), 4.83 (bs, 1 H), 4.50 (q, J=5.2 Hz, 1 H), 3.89 (bs, 1 H), 3.58 (ddd, J=1.2, 3.6, 12.0 Hz, 1 H), 2.62 (bs, 1 H), 2.0 (dt, J=4.4, 17.6 Hz, 1 H), 1.23 (s, 6 H). MS m/z 304.1 (M+23)+.

Workup

  1. extractionThe mixture was extracted with EtOAc
  2. washwashed with water and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe mixture was purified by column chromatography on silica gel with EtOAc/hexanes gradient as eluant

Sources & evidence

ORD record
ord-3b11824cfc6b4a63813c880c248da912
Source dataset
uspto-grants-2015_08
Patent number
US09102671B2

Reaction notes

Loading…