4-Nitrobenzenesulfonyl chloride → trans-Tert-butyl 4-fluoro-5-(4-nitrophenylsulfonyloxy)azepane-1-carboxylate

HRID 876457Notes

Reaction equation

HRID 876457 reaction equation
[F:1][C@H:2]1[C@H:8]([OH:9])[CH2:7][CH2:6][N:5]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:4][CH2:3]1.[N+:17]([C:20]1[CH:25]=[CH:24][C:23]([S:26](Cl)(=[O:28])=[O:27])=[CH:22][CH:21]=1)([O-:19])=[O:18].CCN(CC)CC>C(Cl)Cl>[F:1][C@H:2]1[C@H:8]([O:9][S:26]([C:23]2[CH:22]=[CH:21][C:20]([N+:17]([O-:19])=[O:18])=[CH:25][CH:24]=2)(=[O:27])=[O:28])[CH2:7][CH2:6][N:5]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 74044-Nitrobenzenesulfonyl chlorideHCID 8471TriethylamineHCID 105531513rac-tert-butyl (4R,5R)-4-fluoro-5-hydroxyazepane-1-carboxylate

Product 1

HCID 131731013trans-Tert-butyl 4-fluoro-5-(4-nitrophenylsulfonyloxy)azepane-1-carboxylateYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

trans-tert-butyl 4-fluoro-5-hydroxyazepane-1-carboxylate (12.36 g, 52.98 mmol) was dissolved in CH2Cl2 (110 mL). The solution was cooled to 0° C., 4-nitrobenzene-1-sulfonyl chloride (14.09 g, 63.58 mmol) was added and the mixture was stirred for 10 minutes. NEt3 (11.08 mL, 79.48 mmol) was added and the mixture was slowly warmed to ambient temperature over 1 hour and stirred for an additional 2 hours. The mixture was diluted with CH2Cl2 and washed with water followed by 1N KHSO4 (2×50 mL), then with saturated aqueous NaHCO3 (50 mL) and brine, and the combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified via column chromatography (10 to 70% MTBE/hexanes) to provide 18.4 g of the product (84%) as a single isomer and as a faint orange powder.

Workup

  1. temperaturethe mixture was slowly warmed to ambient temperature over 1 hour
  2. stirringstirred for an additional 2 hours
  3. washwashed with water
  4. dry with materialwith saturated aqueous NaHCO3 (50 mL) and brine, and the combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified via column chromatography (10 to 70% MTBE/hexanes)

Sources & evidence

ORD record
ord-f5b1be35306b4ccca2d7e09e018e50d8
Source dataset
uspto-grants-2015_03
Patent number
US08987251B2

Reaction notes

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