Methyl bromoacetate → (3-(R)-t-Butyldimethylsilyloxymethyl-4-(S)-(3-fluorophenyl)pyrrolidin-1-yl)-acetic Acid, Methyl Ester

HRID 1068247Notes

Reaction equation

[Si:1]([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][NH:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Br[CH2:23][C:24]([O:26][CH3:27])=[O:25].CCN(C(C)C)C(C)C>C(#N)C>[Si:1]([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]([CH2:23][C:24]([O:26][CH3:27])=[O:25])[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 1.0 g (3.23 mmol) of (3-(R)-t-Butyldimethylsilyloxymethyl-4-(S)-(3-fluorophenyl)pyrrolidine in 8 mL of acetonitrile was treated with 0.47 mL (4.95 mmol) of methyl bromoacetate and 0.86 g (4.95 mmol) of DIEA and the reaction was heated in 80° C. bath. After 2 hr, the solution was cooled, and partitioned between water-EtOAc. The organic layer was washed with brine, dried and concentrated. The residue was purified on a flash column using a gradient of 10-20% EtOAc in hexanes to isolate 0.45 g of the title compound. 1H NMR (CDCl3) 0.027 (2s, 6H), 0.87 (s, 9H), 2.4 (m, 1H), 2.7-3.1 (m, 5H), 3.33 and 3.47 (ABq, 2H), 3.63 (m, 2H), 3.76 (s, 3H), 6.8-7.3 (m 4H).

Workup

temperaturethe solution was cooled
custompartitioned between water-EtOAc
washThe organic layer was washed with brine
customdried
concentrationconcentrated
customThe residue was purified on a flash column

Sources & evidence

ORD record: ord-0ea13753d912405ab670406ea3ab4934
Source dataset: uspto-grants-2001_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06248755B1

Reaction notes

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