Triethylamine → HCID 86677105, compound

HRID 1427395Notes

Reaction equation

HRID 1427395 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[C:6]([O:10][C:11](=[O:32])[NH:12][C:13]1[S:14][CH2:15][C@@H:16]2[CH2:22][C@H:21]([CH2:23][OH:24])[O:20][CH2:19][C@:17]2([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[F:31])[N:18]=1)([CH3:9])([CH3:8])[CH3:7].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:1][S:2]([O:24][CH2:23][C@@H:21]1[O:20][CH2:19][C@:17]2([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[F:31])[N:18]=[C:13]([NH:12][C:11]([O:10][C:6]([CH3:9])([CH3:7])[CH3:8])=[O:32])[S:14][CH2:15][C@@H:16]2[CH2:22]1)(=[O:4])=[O:3]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 71278244HCID 71278244, compound

Product 1

HCID 86677105HCID 86677105, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methanesulfonyl chloride (36.2 μL, 0.474 mmol) was added drop-wise to a 0° C. solution of tert-butyl[(4aR,6R,8aS)-8a-(2-fluorophenyl)-6-(hydroxymethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]carbamate (C18) (94 mg, 0.24 mmol) and triethylamine (0.198 mL, 1.42 mmol) in dichloromethane (1 mL). The reaction was allowed to warm to room temperature and stir for 18 hours. Saturated aqueous sodium bicarbonate solution was added, and the mixture was extracted three times with dichloromethane. The combined organic layers were washed with water, washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Silica gel chromatography (Gradient: 0% to 50% ethyl acetate in heptane) provided the product as a white solid. Yield: 86 mg, 0.18 mmol, 75%. LCMS m/z 475.4 (M+1). 1H NMR (400 MHz, CDCl3) δ 1.53 (s, 9H), 1.60-1.68 (br m, 1H), 1.92-2.07 (br m, 1H), 2.56 (dd, J=12.9, 2.9 Hz, 1H), 2.93 (dd, J=12.7, 3.9 Hz, 1H), 3.07-3.19 (br m, 1H), 3.09 (s, 3H), 3.79 (d, J=12.1 Hz, 1H), 3.96-4.04 (m, 1H), 4.21 (dd, J=12.0, 1.5 Hz, 1H), 4.27 (dd, half of ABX pattern, J=11.3, 6.2 Hz, 1H), 4.32-4.38 (br m, 1H), 7.06-7.13 (m, 1H), 7.18-7.24 (m, 1H), 7.30-7.39 (br m, 2H).

Workup

  1. extractionthe mixture was extracted three times with dichloromethane
  2. washThe combined organic layers were washed with water
  3. washwashed with saturated aqueous sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-89391096bb60465ba7190f5a574f04d0
Source dataset
uspto-grants-2015_01
Patent number
US08933221B2

Reaction notes

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