Tetrabutylammonium Fluoride → 2-(R)-(3-(R)-(hydroxymethyl)4-(S)-phenylpyrrolidin-1-yl)-3-(cyclobutyl)propionic acid, benzyl ester

HRID 2301170Notes

Reaction equation

HRID 2301170 reaction equation
[Si]([O:8][CH2:9][C@@H:10]1[C@@H:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:13][N:12]([C@H:21]([CH2:32][CH:33]2[CH2:36][CH2:35][CH2:34]2)[C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH2:11]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[OH:8][CH2:9][C@@H:10]1[C@@H:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:13][N:12]([C@H:21]([CH2:32][CH:33]2[CH2:34][CH2:35][CH2:36]2)[C:22]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)=[O:23])[CH2:11]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 1317226812-(R)-(3-(R)-(t-Butyldimethylsilyloxymethyl)-4-(S)-phenyl-pyrrolidin1-yl)-3-(cyclobutyl)propionic acid, benzyl ester

Product 1

HCID 1317226822-(R)-(3-(R)-(hydroxymethyl)4-(S)-phenylpyrrolidin-1-yl)-3-(cyclobutyl)propionic acid, benzyl esterYield 94.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3.20 g (6.3 mmol) of 2-(R)-(3-(R)-(t-butyldimethylsilyloxymethyl)-4-(S)-phenylpyrrolidin-1-yl)-3-(cyclobutyl) propionic acid, benzyl ester (from Step A) in 40 mL of THF at 0° C. was treated with 10 mL of 1.0 M tetrabutylammonium fluoride solution in THF. The resulting mixture was warmed to rt and stirred for 2.5 h. The reaction mixture was partitioned between 200 mL of ether and 100 mL of 50% sat'd NaHCO3 and the layers were separated. The organic layer was dried over MgSO4 and concentrated. Flash chromatography on 100 g of silica gel using 2:1 v/v hexanes/ether as the eluant afforded 2.34 g (94%) of the title compound: 1H NMR (500 MHz) δ 1.56-2.07 (8H), 2.15 (br s, 1H), 2.27-2.37 (2H), 2.64 (t, J=11.0, 1H), 2.80 (dd, J=6.5, 11.0), 3.04-3.11 (2H), 3.23-3.30 (2H), 3.56 (dd, J=7.5, 13.0, 1H), 3.68 (dd, J=5.5, 13.0, 1H), 5.15 (ABq, J=20.0, 2H), 7.17-7.40 (10H).

Workup

  1. customThe reaction mixture was partitioned between 200 mL of ether and 100 mL of 50%
  2. customthe layers were separated
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-84655c41e2b540dbb813541affa287ba
Source dataset
uspto-grants-2002_12
Patent number
US06498161B1

Reaction notes

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