Methyl chloroformate → (S)-2-(Methoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acid
Reaction equation
[NH2:1][C@@H:2]([CH:6]1[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1)[C:3]([OH:5])=[O:4].C(=O)([O-])[O-].[Na+].[Na+].Cl[C:19]([O:21][CH3:22])=[O:20]>O>[CH3:22][O:21][C:19]([NH:1][C@@H:2]([CH:6]1[CH2:7][CH2:8][O:9][CH2:10][CH2:11]1)[C:3]([OH:5])=[O:4])=[O:20]Participants
Procedure
To (S)-2-amino-2-(tetrahydro-2H-pyran-4-yl)acetic acid (505 mg; 3.18 mmol; obtained from Astatech) in water (15 ml) was added sodium carbonate (673 mg; 6.35 mmol), and the resultant mixture was cooled to 0° C. and then methyl chloroformate (0.26 ml; 3.33 mmol) was added dropwise over 5 minutes. The reaction was allowed to stir for 18 hours while allowing the bath to thaw to ambient temperature. The reaction mixture was then partitioned between 1N HCl and ethyl acetate. The organic layer was removed and the aqueous layer was further extracted with 2 additional portions of ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo to afford Cap-170a colorless residue. 1H NMR (500 MHz, DMSO-d6) δ ppm 12.65 (1H, br s), 7.44 (1H, d, J=8.24 Hz), 3.77-3.95 (3H, m), 3.54 (3H, s), 3.11-3.26 (2H, m), 1.82-1.95 (1H, m), 1.41-1.55 (2H, m), 1.21-1.39 (2H, m); LC-MS: Anal. Calcd. for [M+H]+ C9H16NO5: 218.1; found 218.1.
Workup
- customthaw to ambient temperature
- customThe reaction mixture was then partitioned between 1N HCl and ethyl acetate
- customThe organic layer was removed
- extractionthe aqueous layer was further extracted with 2 additional portions of ethyl acetate
- washThe combined organic layers were washed with brine
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customto afford Cap-170a colorless residue
Sources & evidence
- ORD record
- ord-11e0e694c4a24092b70b2baafbade048
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08362020B2
Reaction notes
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