2-Propenoic acid, 3-phenyl-, methyl ester → HCID 11416221, compound

HRID 1107050Notes

Reaction equation

HRID 1107050 reaction equation
[OH-].[Na+].[C:3](=[O:13])([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[NH2:4].Cl[O:15]C(C)(C)C.[C:20]([O:30][CH3:31])(=[O:29])[CH:21]=[CH:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>O.CC[C@H]1[C@@H]2C[C@H]([C@@H](OC3C=CC(O[C@@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@@H](CC)[C@@H](CC5)C4)=C4C(C5C(C(=O)C=34)=CC=CC=5)=O)C3C=CN=C4C=3C=C(OC)C=C4)N(CC2)C1.CCCCCC.CCOC(C)=O.C(O)CC>[CH3:31][O:30][C:20](=[O:29])[C@H:21]([C@@H:22]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[OH:15])[NH:4][C:3]([O:5][CH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)=[O:13]

Participants

9

Reactant 4

HCID 76442-Propenoic acid, 3-phenyl-, methyl esterHCID 12136Benzyl carbamateHCID 14798Sodium HydroxideHCID 521297Tert-Butyl hypochlorite

Product 1

HCID 11416221HCID 11416221, compoundYield 62.5%

Reagents, catalysts & solvents 4

HCID 71311419HCID 71311419, compoundCatalystHCID 962WaterSolventHCID 10311-PropanolSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a reaction flask immersed in a water bath was charged with sodium hydroxide (3.05 mmol of a commercial 1.022 N solution) and diluted with water (4.5 mL) in a dark fume hood. Part of this alkaline solution (c. 0.5 mL)4b was transferred into a vial to dissolve K2 [OsO2 (OH)4 ] (14.7 mg, 0.04 mmol). With vigorous stirring, n-propanol (4 mL) and benzyl carbamate (0.469 g, 3.1 mmol) were added to the flask, followed by dropwise addition of freshly prepared t-butyl hypochlorite (0.331 g, 0.346 mL, 3.05 mmol). After five minutes, an n-propanol solution (3.5 mL) of (DHQD)2AQN (34.3 mg, 0.04 mmol) (Aldrich cat. no.: 45,671-3) and methyl cinnamate (0.162 g, 1 mmol), and the aqueous K2 [OsO2 (OH)4 ] solution were added. After 1.5 h, the solution was quenched with 0.5 g sodium bisulfite. After the usual workup (Li, G.; Angert, H. H.; Sharpless, K. B. Angew. Chem. Tnt. Ed. Engl. 1996, 35, 2813-2817), 0.206 g (62% yield, 92% ee) of the pure (2S,3R)-N-benzyloxycarbonyl-3-phenylserine methyl ester (B, entry 1, R=H) was isolated via chromatography on silica gel (hexane/EtOAc=5:1, A elutes before B).(2S,3R)-B, R=H: M.p. 107-108° C.; [a]o(25,D)=-26.9 (c=1 in 95% EtOH); 1H-NMR (400 MHz, CDCl3): d=7.35-7.23 (m, 10 H), 5.55 (d, J=8.5 Hz, 1H), 5.38 (s, 1H), 4.99 (s, 2H), 4.59 (dd, J=2.5, 9.1 Hz, 1H), 3.75 (s, 3H), 2.56 (br s, 1H); 13C-NMR (150 MHz, CDCl3) : d=171.1, 158.9, 139.5, 136.1, 128.5, 128.2, 128.1, 127.9, 126.2, 125.9, 73.7, 67.0, 59.7, 52.7; HRMS calcd. for C18H19NO5 (M+Na)+ : 352.1161, found: 352.1152; HPLC: Chiralcel OD-H, 0.46 cm×25 cm, hexane/i-PrOH 85/15, 0.6 mL/min, 210 nm, 30.1 min (2R,3S), 33.7 min (2S, 3R). The absolute configuration of this compound was determined by hydrogenolytic removal of the CBz-group, followed by comparison of the resulting aminohydroxyester's optical rotation with the literature value; Beulshausen et al. Liebigs Ann. Chem. 1991, 1207-1209.

Workup

  1. customTo a reaction flask immersed in a water bath
  2. waitAfter 1.5 h
  3. customthe solution was quenched with 0.5 g sodium bisulfite

Sources & evidence

ORD record
ord-943ee8a9a2804e2da32a33a280a71059
Source dataset
uspto-grants-2000_05
Patent number
US06057473

Reaction notes

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