1,2-Dichloroethane → tert-Butyl 4-{[(3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-phenylpyrrolidin-1-yl]carbonyl}-2,2-dimethyl-1,3-oxazolidine-3-carboxylate

HRID 2377036Notes

Reaction equation

HRID 2377036 reaction equation
[F:1][C:2]([F:28])([F:27])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@@H:16]2[C@@H:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:19][NH:18][CH2:17]2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C1C=CC2N(O)N=NC=2C=1.[C:39]([O:43][C:44]([N:46]1[CH:50]([C:51](O)=[O:52])[CH2:49][O:48][C:47]1([CH3:55])[CH3:54])=[O:45])([CH3:42])([CH3:41])[CH3:40].C(N(CC)CC)C.C(Cl)CCl>C(Cl)Cl>[F:11][C:9]([F:12])([F:10])[C:7]1[CH:6]=[C:5]([C@H:13]([O:15][C@@H:16]2[C@@H:20]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:19][N:18]([C:51]([CH:50]3[CH2:49][O:48][C:47]([CH3:55])([CH3:54])[N:46]3[C:44]([O:43][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:45])=[O:52])[CH2:17]2)[CH3:14])[CH:4]=[C:3]([C:2]([F:27])([F:1])[F:28])[CH:8]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 28162763-(Tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidine-4-carboxylic acidHCID 86610912(3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-phenylpyrrolidine

Product 1

HCID 11433611tert-Butyl 4-{[(3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-phenylpyrrolidin-1-yl]carbonyl}-2,2-dimethyl-1,3-oxazolidine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 38 mg (0.094 mmol) (3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-phenylpyrrolidine (Example 1. Step E) in 7.5 mL methylene chloride was added 12.7 mg (0.094 mmol) HOBT, 34.7 mg (0.14 mmol) 3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidine-4-carboxylic acid, 0.04 mL (0.28 mmol) triethylamine and 54 mg (0.28 mmol) EDC. The resulting mixture was stirred at RT for 16 hr. The reaction mixture was partitioned between 5 mL brine and extracted with EtOAc (3×5 mL). The combined organic layers were dried over sodium sulfate, filtered and the solvent removed under vacuum. The yellow oil was purified by prep TLC eluting with methylene chloride/methanol (95/5) to give the title compound. 1H-NMR (CDCl3) rotamers: δ: 1.4-1.8 (m, 18H), 3.20-3.70 (m, 2H), 3.88-4.3 (m, 3H), 4.43-4.70 (m, 1H), 6.97-7.10 (m, 2H), 7.20-7.35 (m, 3H), 7.53. 7.55, 7.62 (3s, 2H), 7.75, 7.78 (2s, 1H)ppm. MS: 631.3 (MH+) observed.

Workup

  1. customThe reaction mixture was partitioned between 5 mL brine
  2. extractionextracted with EtOAc (3×5 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. customthe solvent removed under vacuum
  6. customThe yellow oil was purified by prep TLC
  7. washeluting with methylene chloride/methanol (95/5)

Sources & evidence

ORD record
ord-a0135ab9034448d0914075e04f251a2c
Source dataset
uspto-grants-2008_12
Patent number
US07468437B2

Reaction notes

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