Phosgene → 4-{[(3R,4S)-3-({(1R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethyl}oxy)-4-phenylpyrrolidin-1-yl]carbonyl}-1,3-oxazolidin-2-one

HRID 2377038Notes

Reaction equation

[NH2:1][CH:2]([C:5]([N:7]1[CH2:11][C@H:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C@@H:9]([O:18][C@@H:19]([C:21]2[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=2)[CH3:20])[CH2:8]1)=[O:6])[CH2:3][OH:4].C(N(CC)CC)C.[C:42](Cl)(Cl)=[O:43]>C(Cl)Cl.C1(C)C=CC=CC=1>[F:33][C:31]([F:34])([F:32])[C:23]1[CH:22]=[C:21]([C@H:19]([O:18][C@@H:9]2[C@@H:10]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:11][N:7]([C:5]([CH:2]3[CH2:3][O:4][C:42](=[O:43])[NH:1]3)=[O:6])[CH2:8]2)[CH3:20])[CH:26]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:24]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 15 mg (0.03 mmol) 2-amino-3-[(3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-phenylpyrrolidin-1-yl]-3-oxopropan-1-ol (Example 5) in 3 mL methylene chloride was added 0.011 mL (0.08 mmol) triethylamine. The resulting mixture was cooled to 0° C. and 0.015 mL (0.03 mmol) of a 2M solution of phosgene in toluene was added by syringe. The reaction mixture was stirred at RT for 8 hr and the volatiles were removed under vacuum. The dark yellow residue was purified by prep TLC eluting with methylene chloride/methanol (95/5) to afford the title compound. 1H-NMR (CDCl3) rotamers: δ: 1.43 (d, 3H, 6.5 Hz), 3.30-4.13 (m, 7H), 4.40-4.70 (m, 3H), 7.00-7.10 (m, 2H), 7.20-7.30 (m, 3H), 7.55 (s, 2H), 7.60 (s, 1H), 7.75, 7.77 (2s, 1H)ppm. MS: 517.0 (MH+) observed.

Workup

customthe volatiles were removed under vacuum
customThe dark yellow residue was purified by prep TLC
washeluting with methylene chloride/methanol (95/5)

Sources & evidence

ORD record: ord-1f9637ea0bb84511b0efbbcec9b2fb51
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07468437B2

Reaction notes

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