H-ALPHA-ME-D-PRO-OH

(R)-α-Methylprolinamide (0.40 g, purity 58percent, 1.78 mmol) obtained in Reference Example 4 and 6 M hydrochloric acid (2 ml) were charged in a flask, and the mixture was reacted at 90°C for 4 hr. As a result of HPLC analysis, it contained (R)-α-methylproline (204 mg, 1.58 mmol, yield 90percent) with optical purity 89percent ee.Preparation of (7aR)-7a-methyltetrahydro-1H, 3H-pyrrolo[1, 2-c][1, 3]oxazole-1, 3-dione (Compound of Formula (5)) Using CDI as Carbonylating Agent) Carbonyldiimidazole (99%, 19.02 g, 116.14 mmol) was charged to a suspension of the compound of Formula (6) (5.0 g, 38.71 mmol), imidazole hydrochloride (12.95 g, 123.88 mmol), and dichloromethane (100 mL) at 0-5 C. After stirring at 0-5 C. for 3.5 hours, the reaction was deemed complete by 1H-NMR analysis (an aliquot was concentrated to dryness and dissolved in CDCl3 to show complete consumption of the compound of Formula (6)), and was comprised of the compound of Formula (5) and the dimer of Formula (5') in a molar ratio of 96:4. The reaction suspension was filtered under a nitrogen stream to remove imidazole by-products, and the filter cake was washed with cold (0-5 C.) dichloromethane (10 mL). The filtrate was washed with a solution (5 wt %) of aqueous citric acid (2*50 mL) where the evolution of gas was observed. The organic layer was then separated, dried over anhydrous sodium sulfate, and concentrated in vacuo at 30-35 C. to afford the compound of Formula (5) as a white solid (4.89 g, 81% yield). 1H-NMR compound of Formula (5): (CDCl3, 300 MHz) delta: 1.54 (3H, s), 1.92-2.13 (2H, m), 2.15-2.27 (2H, m), 3.34 (1H, ddd, J=6.9 Hz, 6.9 Hz, 11.8 Hz), 3.83 (1H, ddd, J=7.7 Hz, 7.7 Hz, 11.5 Hz). 1H-NMR compound of Formula (5'): (CDCl3, 300 MHz) delta: 1.51 (6H, s), 1.94-2.18 (8H, m), 3.43-3.55 (2H, m), 3.72-3.85 (2H, m).

(R)-2-Methyl Proline is a derivative of D-Proline (P755990) which is used in the synthesis of (R)-(+)-N-Boc-Pipecolic Acid, (S)-(-)-Coniine, (S)-(+)-Pelletierine, (+)-.beta.-Conhydrine, and (S)-(-)-Ropivacaine and formal synthesis of (-)-Lasubine II and (+)-Cermizine C.

Molecular Weight:129.16
XLogP3:-2.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:129.078978594
Monoisotopic Mass:129.078978594
Topological Polar Surface Area:49.3
Heavy Atom Count:9
Complexity:135
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes