Triethylamine → Benzyl(3S,4S)-3-[(tert-butoxycarbonyl)amino]-4-{[(methylsulfonyl)oxy]methyl}-1-pyrrolidinecarboxylate

HRID 1817005Notes

Reaction equation

HRID 1817005 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[C@@H:13]([CH2:14][OH:15])[CH2:12][N:11]([C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:33][S:34](Cl)(=[O:36])=[O:35]>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C@H:9]1[C@@H:13]([CH2:14][O:15][S:34]([CH3:33])(=[O:36])=[O:35])[CH2:12][N:11]([C:16]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:17])[CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 23635905(3S,4S)-Benzyl 3-((tert-butoxycarbonyl)amino)-4-(hydroxymethyl)pyrrolidine-1-carboxylate

Product 1

HCID 59693055Benzyl(3S,4S)-3-[(tert-butoxycarbonyl)amino]-4-{[(methylsulfonyl)oxy]methyl}-1-pyrrolidinecarboxylateYield 97.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The product of Example 52B (43.7 g, 125 mmol) and triethylamine (25.2 g, 250 mmol) in CH2Cl2 (600 mL) was treated with methanesulfonyl chloride (12.6 mL, 163 mmol) over 30 minutes at −10° C. The solution was allowed to warm to room temperature over 1 hour and then quenched with water (100 mL). The layers were separated and the aqueous phase was extracted with CH2C2(2×400 mL). The combined organic phases were washed with brine (2×100 mL), dried over Na2SO4, filtered and the filtrate concentrated to provide the title compound as a brown dark brown oil (52.0 g, yield, 97%). 1H NMR (CDCl3, 300 MHz) δ 1.46 (s, 9H), 2.80 (m, 1H), 3.08 (s, 3H), 3.40 (m, 2H), 3.70 (m, 2H), 4.10 (m, 1H), 4.40 (m, 2H), 4.75 (m, 1H), 5.16 (s, 2H), 7.30 m, 5H); MS (DCI/NH3) m/z 446 (M+NH4)+, 429 (M+H)+.

Workup

  1. customquenched with water (100 mL)
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with CH2C2(2×400 mL)
  4. washThe combined organic phases were washed with brine (2×100 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated

Sources & evidence

ORD record
ord-833f801763634c78b6c4ceb9331e87ea
Source dataset
uspto-grants-2009_10
Patent number
US07598236B2

Reaction notes

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