4-Methylmorpholine → (2R,3R)-3-Hydroxy-2-(4-phenylcyclohexylmethyl)butanoic Acid 2-Tetrahydropyranyloxyamide

HRID 2269351Notes

Reaction equation

[OH:1][C@H:2]([CH3:20])[C@@H:3]([CH2:7][CH:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)[C:4]([OH:6])=O.[O:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH:22]1[O:27][NH2:28].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C>[O:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH:22]1[O:27][NH:28][C:4](=[O:6])[C@H:3]([CH2:7][CH:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)[C@H:2]([OH:1])[CH3:20]

Participants

Conditions

Temperature: 25 °C

Procedure

A mixture of (2R,3R)-3-hydroxy-2-(4-phenylcyclohexylmethyl)butanoic acid (3.43 g, 0.012 mol), 2-tetrahydropyranyloxyamine (1.64 g, 0.014 mol), BOP (5.75 g, 0.013 mol), HOBt (1.76 g, 0.13 mol) and NMM (2.63 g, 0.026 mol) in DMF (30 mL) is stirred at 25° C. for 18 h. The mixture is concentrated in vacuo and the residue is taken up in EtOAc. The mixture is washed with ice-cold 0.1 M HCl, saturated aqueous sodium bicarbonate, and saturated aquesous sodium chloride. The organic phase is dried over sodium sulfate and concentrated in vacuo to give 6.02 g of a white solid. Chromatography on silica gel using EtOAc as eluent gives 4.05 g (90%) of (2R,3R)-3-hydroxy-2-(4-phenylcyclohe,(ylmethyl)butanoic acid 2-tetrahydropyranyloxyamide as a white solid.

Workup

concentrationThe mixture is concentrated in vacuo
washThe mixture is washed with ice-cold 0.1 M HCl, saturated aqueous sodium bicarbonate, and saturated aquesous sodium chloride
dry with materialThe organic phase is dried over sodium sulfate
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-4d75db90fea4441db81518d9fc7dc79c
Source dataset: uspto-grants-2001_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06329400B1

Reaction notes

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