Formaldehyde → L-Proline, N,N-dimethylglycyl-4-(benzoylamino)-, (4R)-

HRID 913202Notes

Reaction equation

N[CH2:2][C:3]([N:5]1[CH2:9][C@H:8]([NH:10][C:11](=[O:18])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:7][C@H:6]1[C:19]([OH:21])=[O:20])=[O:4].[CH2:22]=O.[C:24]([BH3-])#[N:25].[Na+]>CO>[C:11]([NH:10][C@H:8]1[CH2:9][N:5]([C:3](=[O:4])[CH2:2][N:25]([CH3:24])[CH3:22])[C@H:6]([C:19]([OH:21])=[O:20])[CH2:7]1)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (2S4R)1-(2-Amino-acetyl)-4-benzoylamino-pyrrolidine-2-carboxylic acid (Compound 2, 0.05 g, 0.17 mmol) in methanol (3 mL) at room temperature was added 37% aqueous formaldehyde (Aldrich) (0.1 mL). The resulting mixture was stirred at this temperature for 3 hours, then cooled to 0° C., and sodium cyanoborohydride (Aldrich) (0.043 g, 0.69 mmol, 4 equivalents) was added portion-wise over 5 minutes. After stirring for 1 hour at room temperature, the solvent was removed in vacuo and the solid residue was purified by preparative HPLC (column: XTerra MS C18, 5 u, 19×150 mm) using 5% to 95% methanol/water gradient (0.1% formic acid in methanol and 0.1% formic acid in water) to afford 0.017 g (31% yield) of the desired product.

Workup

stirringAfter stirring for 1 hour at room temperature
customthe solvent was removed in vacuo
customthe solid residue was purified by preparative HPLC (column: XTerra MS C18, 5 u, 19×150 mm)

Sources & evidence

ORD record: ord-e6f7b49b19174f3890200aedcde361e9
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026272B2

Reaction notes

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