Tetrabutylammonium Fluoride → alpha-(R)-(3-(R)-(Hydroxymethyl)-4-(S)-(3-fluorophenyl)-pyrrolidin-1-yl)-isopropylacetic Acid, Para-methoxybenzyl Ester

HRID 1068126Notes

Reaction equation

HRID 1068126 reaction equation
[Si]([O:8][CH2:9][C@H:10]1[C@@H:14]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)[CH2:13][N:12]([C@H:22]([CH:35]([CH3:37])[CH3:36])[C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)=[O:24])[CH2:11]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si](OC[C@@H]1[C@@H](C2C=CC=CC=2)CNC1)(C(C)(C)C)(C)C>C1COCC1>[OH:8][CH2:9][C@@H:10]1[C@@H:14]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)[CH2:13][N:12]([C@H:22]([CH:35]([CH3:37])[CH3:36])[C:23]([O:25][CH2:26][C:27]2[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=2)=[O:24])[CH2:11]1

Participants

5

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 21341073(3R,4S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-phenylpyrrolidineHCID 131722689alpha-(R)-(3-(S)-((tert-butyldimethylsilyloxy)methyl)-4-(S)-(3-fluorophenyl)-pyrrolidin-1-yl)-isopropylacetic acid, para-methoxybenzyl ester

Product 1

HCID 131722688alpha-(R)-(3-(R)-(Hydroxymethyl)-4-(S)-(3-fluorophenyl)-pyrrolidin-1-yl)-isopropylacetic Acid, Para-methoxybenzyl EsterYield 92.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The title compound was prepared from 14.84 g of α-(R)-(3-(S)-((tert-butyldimethylsilyloxy)methyl)-4-(S)-(3-fluorophenyl)-pyrrolidin-1-yl)-isopropylacetic acid, para-methoxybenzyl ester (from Step B above) and 125 mL of 1M solution of tetrabutylammonium fluoride in 125 mL of THF using a procedure analogous to that described in Example 1, Step B, Aldehyde 1. After purification with flash chromatography on silica gel, 10.75 g of the title compound was obtained as a colorless oil. RF: 0.23 (30% EtOAc in hexanes with 1% (v/v) Et3N). 1H NMR (500 MHz, CDCl3): δ7.33˜7.36 (m, 2H), 7.22˜7.26 (m, 1H), 6.88˜6.98 (m, 5H), 5.14 (AB d, 12.3 Hz, 1H), 5.13 (AB d, 12.3 Hz, 1H), 3.82 (s, 3H), 3.68 (dd, 4.6 & 10.6 Hz, 1H), 3.57 (dd, 6.1 & 10.5 Hz, 1H), 3.25˜3.29 (m, 1H), 3.05˜3.16 (m, 3H), 2.73˜2.77 (m, 1H), 2.60˜2.64 (m, 1H), 2.29˜2.35 (m, 1H), 2.02˜2.10 (m, 1H), 1.03 (d, 6.6 Hz, 3H), 0.91 (d, 6.7 Hz, 3H).

Workup

  1. customAfter purification with flash chromatography on silica gel

Sources & evidence

ORD record
ord-748c370d55754946b6fe93aaa508ca13
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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