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

HRID 2035621Notes

Reaction equation

HRID 2035621 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-9e8996505fda4004bed30c44187d57b5
Source dataset
uspto-grants-2013_11
Patent number
US08575145B2

Reaction notes

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