Tetrabutylammonium Fluoride → (2R,4R)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4-hydroxypyrrolidine-1-carboxylate

HRID 513013Notes

Reaction equation

HRID 513013 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]=[C:25]([F:27])[CH:24]=[C:23]([C:28]#[N:29])[CH:22]=2)[CH2:10]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:28]([C:23]1[CH:22]=[C:21]([C@H: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]=[C:25]([F:27])[CH:24]=1)#[N:29].[C:28]([C:23]1[CH:22]=[C:21]([C@@H: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]=[C:25]([F:27])[CH:24]=1)#[N:29]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 66688415(4R)-tert-butyl 4-((tert-butyldimethylsilyl)oxy)-2-(3-cyano-5-fluorophenyl)pyrrolidine-1-carboxylate

Product 2

HCID 66691632(2R,4R)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4-hydroxypyrrolidine-1-carboxylateHCID 68282616(2S,4R)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4-hydroxypyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (4R)-tert-butyl 4-((tert-butyldimethylsilyl)oxy)-2-(3-cyano-5-fluorophenyl)pyrrolidine-1-carboxylate (I-12) (2.7 g, 6.4 mmol) in THF (25 mL) at room temperature was added TBAF (7.1 mL of a 1.0 M solution in THF, 7.0 mmol). The mixture was stirred at room temperature for 1 hour then concentrated. The mixture was purified by column chromatography on silica gel with EtOAc/hexanes gradient as eluant to yield the desired isomer (2R,4R)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4-hydroxypyrrolidine-1-carboxylate (I-13A) and (2S,4R)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4-hydroxypyrrolidine-1-carboxylate (I-13B). 1H NMR (400 MHz, CDCl3) δ 7.41 (s, 1 H), 7.35-7.26 (m, 1 H), 7.24-7.16 (m, 1 H), 4.89 (d, J=48.8 Hz, 1 H), 4.56-4.50 (m, 1 H), 3.85-3.70 (m, 1 H), 3.66-3.55 (m, 1 H), 2.59 (bs, 1 H), 2.00-1.90 (m, 1 H), 1.45 (bs, 3 H), 1.22 (bs, 6 H). MS m/z 304.1 (M+23)+.

Workup

  1. concentrationthen concentrated
  2. customThe mixture was purified by column chromatography on silica gel with EtOAc/hexanes gradient as eluant

Sources & evidence

ORD record
ord-bd3fb39bec014c028067039ba12f9f1d
Source dataset
uspto-grants-2015_08
Patent number
US09102671B2

Reaction notes

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