Trimethyl borate → 1-N-Boc-pyrrolidin-2-ylboronic acid

HRID 748639Notes

Reaction equation

HRID 748639 reaction equation
[N:1]1([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.C([Li])(CC)C.C[O:19][B:20](OC)[O:21]C>C1COCC1>[B:20]([OH:21])([OH:19])[CH:5]1[N:1]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:2][CH2:3][CH2:4]1

Participants

5

Reactant 3

HCID 8470Trimethyl borateHCID 643455N-Boc-pyrrolidineHCID 178418400CID 53628100

Product 1

HCID 27625251-N-Boc-pyrrolidin-2-ylboronic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-acetyl-gly-boroproline 5 was prepared according to the synthetic route of FIG. 1. Metallation of tert-butyl 1-pyrrolidinecarboxylate (N-t-BOC-pyrrolidine, Sigma-Aldrich Co.) in THF with sec-butyllithium, followed by addition of trimethylborate gave 1-(tert-butoxycarbonyl)pyrrolidin-2-yl-2-boronic acid 1 after quenching with aqueous NaOH and extraction. Borate esterification with the (1S, 2S, 3R, 5S), (+)-pinanediol in methyl, tert-butyl ether (MTBE) gave borate ester 2. Acid hydrolysis of the BOC protecting group and selective crystallization in isopropyl alcohol gave (+)-pinane 1-pyrrolidin-2-yl-2-boronate 3. Coupling of 3 and N-acetyl glycine with EDC (N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide), HOBt (1-hydroxybenzotriazole), and DiPEA (diisopropylethylamine gave the pinane borate of N-acetyl-gly-boroproline 4. Borate exchange of 4 with phenylboronic acid in MTBE and water gave N-acetyl-gly-boroproline 5.

Sources & evidence

ORD record
ord-795ec57553d8499cbb845577b77d9ebd
Source dataset
uspto-grants-2008_07
Patent number
US07399869B2

Reaction notes

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