Potassium tert-butoxide → 1-(3-Benzyloxy-propyl)-4a-(4-chloro-benzenesulfonyl)-5,8-difluoro-2,3,4,4a,10,10a-hexahydro-1H-9-oxa-1-aza-phenanthrene

HRID 564337Notes

Reaction equation

HRID 564337 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][N:12]([CH:21]1[CH:30]([S:31]([C:34]2[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=2)(=[O:33])=[O:32])[C:29]2[C:24](=[C:25]([F:42])[CH:26]=[CH:27][C:28]=2[F:41])[O:23][CH2:22]1)[CH2:13][CH2:14][CH2:15]OS(C)(=O)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+]>C1COCC1>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][N:12]1[CH:21]2[C:30]([S:31]([C:34]3[CH:35]=[CH:36][C:37]([Cl:40])=[CH:38][CH:39]=3)(=[O:33])=[O:32])([C:29]3[C:24]([O:23][CH2:22]2)=[C:25]([F:42])[CH:26]=[CH:27][C:28]=3[F:41])[CH2:15][CH2:14][CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 86614616HCID 86614616, compound

Product 1

HCID 670062721-(3-Benzyloxy-propyl)-4a-(4-chloro-benzenesulfonyl)-5,8-difluoro-2,3,4,4a,10,10a-hexahydro-1H-9-oxa-1-aza-phenanthrene

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The Methanesulfonic acid 3-{(3-benzyloxy-propyl)-[4-(4-chloro-benzenesulfonyl)-5,8-difluoro-chroman-3-yl]-amino}-propyl ester was dissolved in 60 mL of THF then potassium tertbutoxide (1M solution in tertbutanol, 3.27 ml, 3.27 mmol) was added and the reaction was stirred at room temperature for 1 h. The reaction was quenched with 100 ml of brine and 100 ml of ethyl acetate. The layers were separated and the organic layer was dried over sodium sulfate then concentrated. The product was purified by column using EtOAc/Hex. as the eluent (gradient from 0/100 to 100/0 in 35 minutes). Yield: 438.8 mg, 80. 1H NMR (CDCl3 400 MHz) δ7.61 (d, J=8.1 Hz, 2H), 7.48 (d, J=8.8 Hz, 2H), 7.37-7.24 (m, 5H), 7.04 (td, 9.5, 5.1 Hz, 1H), 6.43-6.36 (m, 1H), 5.14 (d, J=12.4 Hz, 1H), 4.72 (d, J=13.9 Hz, 1H), 4.47 (dd, J=28.5, 11.7 Hz, 2H), 3.42 (t, J=6.2 Hz, 2H), 3.29 (s, 1H), 2.90-2.82 (m, 2H), 2.82-2.75 (m, 1H), 2.57 (d, 12.4 Hz, 1H), 2.45 (td, J=11.7, 2.2 Hz, 1H), 2.03-1.93 (m, 1H), 1.83-1.64 (m, 2H), 1.63-1.59 (m, 1H), 1.36-1.23 (m, 1H).

Workup

  1. customThe reaction was quenched with 100 ml of brine and 100 ml of ethyl acetate
  2. customThe layers were separated
  3. dry with materialthe organic layer was dried over sodium sulfate
  4. concentrationthen concentrated
  5. customThe product was purified by column
  6. customas the eluent (gradient from 0/100 to 100/0 in 35 minutes)

Sources & evidence

ORD record
ord-f291cb1f37ff4486bd7b061219d0f649
Source dataset
uspto-grants-2011_11
Patent number
US08067621B2

Reaction notes

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