Triethylamine → (+/-)-N-Boc-trans-3-(4-phenylbenzenesulfonamido)-4-hydroxypyrrolidine

HRID 1952433Notes

Reaction equation

HRID 1952433 reaction equation
C(NCCCCCC(N1C[C@@H](S)[C@H](N[S:19]([C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:24][CH:23]=2)(=[O:21])=[O:20])C1)=O)(=O)C.[C:34]([N:41]1[CH2:45][C@@H:44]([OH:46])[C@H:43]([N:47]=[N+]=[N-])[CH2:42]1)([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(N(CC)CC)C.C1(C2C=CC(S(Cl)(=O)=O)=CC=2)C=CC=CC=1>C1COCC1.O.CCCCCC.C1COCC1.C(OCC)(=O)C>[C:34]([N:41]1[CH2:45][C@@H:44]([OH:46])[C@H:43]([NH:47][S:19]([C:22]2[CH:23]=[CH:24][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:26][CH:27]=2)(=[O:21])=[O:20])[CH2:42]1)([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35]

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 74192(1,1'-Biphenyl)-4-sulphonyl chlorideHCID 15855750Tert-butyl (3R,4R)-3-azido-4-hydroxypyrrolidine-1-carboxylateHCID 86654491(+/-)-N-(6-Acetamidohexanoyl)-trans-3-(4-phenylbenzene-sulfonamido)-4-mercaptopyrrolidine

Product 1

HCID 86654490(+/-)-N-Boc-trans-3-(4-phenylbenzenesulfonamido)-4-hydroxypyrrolidineYield 73.5%

Reagents, catalysts & solvents 4

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
65 °C

Procedure

(±)-N-(6-Acetamidohexanoyl)-trans-3-(4-phenylbenzene-sulfonamido)-4-mercaptopyrrolidine. To a solution of (±)-N-Boc-trans-3-azido-4-hydroxypyrrolidine (228 mg, 1.0 mmol) in THF—H2O (10:1, 5 mL) was added Ph3P (275 mg, 1.05 mmol), and the mixture was stirred at room temperature for 2 hr and at 65° C. until no starting material was detected on TLC (25% ethyl acetate in hexane). The solution was cooled with stirring to 0° C., and triethylamine (167 μL, 1.2 mmol) was added, then a solution of 4-phenylbenzenesulfonyl chloride (256 mg, 1.1 mmol) in THF (2 mL) was added dropwise. The reaction mixture was warmed to room temperature and was stirred for 3 hr. The mixture was concentrated under reduced pressure, ethyl acetate was added to the residue and the organic layer was washed with 10% aq citric acid and sat. aq NaHCO3, then it was dried over Na2SO4 and evaporated. The residue was purified by flash chromatography (50% ethyl acetate in hexane) to give (±)-N-Boc-trans-3-(4-phenylbenzenesulfonamido)-4-hydroxypyrrolidine (337 mg, 73.5%): 1H NMR (300 MHz, CDCl3+CD3OD) δ 7.88 (d, J=8, 2H), 7.69 (d, J=8, 2H), 7.56 (d, J=8, 2H), 7.41 (m, 3H), 4.06 & 4.20 (br m, 1H), 3.52 (br m, 3H), 3.12 (m, 2H), 1.36 & 1.38 (s, 9H); HRMS (ESI) calculated for C21H26N2O5SNa+441.1460. found 441.1469.

Workup

  1. temperatureThe solution was cooled
  2. stirringwith stirring to 0° C.
  3. temperatureThe reaction mixture was warmed to room temperature
  4. stirringwas stirred for 3 hr
  5. concentrationThe mixture was concentrated under reduced pressure, ethyl acetate
  6. additionwas added to the residue
  7. washthe organic layer was washed with 10% aq citric acid and sat. aq NaHCO3
  8. dry with materialit was dried over Na2SO4
  9. customevaporated
  10. customThe residue was purified by flash chromatography (50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-54ae9e912e654f0681db1058125c3b43
Source dataset
uspto-grants-2013_03
Patent number
US08404866B2

Reaction notes

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