Triethylamine → isobutyric acid (1S,2S)-6-fluoro-2-[2-({3-[(2-fluoro-ethyl)-(3-methoxy-2-methoxymethyl-2-methyl-propyl)-amino]-propyl}-methyl-amino)-ethyl]-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-yl ester

HRID 2090573Notes

Reaction equation

HRID 2090573 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([CH:12]([CH3:14])[CH3:13])[C@:7]([CH2:16][CH2:17][N:18]([CH2:20][CH2:21][CH2:22][N:23]([CH2:33][CH2:34][F:35])[CH2:24][C:25]([CH2:30][O:31][CH3:32])([CH3:29])[CH2:26][O:27][CH3:28])[CH3:19])([OH:15])[CH2:6][CH2:5]2.CCN(CC)CC.[C:43](Cl)(=[O:47])[CH:44]([CH3:46])[CH3:45]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([CH:12]([CH3:13])[CH3:14])[C@@:7]([O:15][C:43](=[O:47])[CH:44]([CH3:46])[CH3:45])([CH2:16][CH2:17][N:18]([CH2:20][CH2:21][CH2:22][N:23]([CH2:33][CH2:34][F:35])[CH2:24][C:25]([CH2:26][O:27][CH3:28])([CH3:29])[CH2:30][O:31][CH3:32])[CH3:19])[CH2:6][CH2:5]2

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62325Isobutyryl chlorideHCID 45381135(1S,2S)-6-fluoro-2-[2-({3-[(2-fluoro-ethyl)-(3-methoxy-2-methoxymethyl-2-methyl-propyl)-amino]-propyl}-methyl-amino)-ethyl]-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-ol

Product 1

HCID 45381136isobutyric acid (1S,2S)-6-fluoro-2-[2-({3-[(2-fluoro-ethyl)-(3-methoxy-2-methoxymethyl-2-methyl-propyl)-amino]-propyl}-methyl-amino)-ethyl]-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-yl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 398 mg of (1S,2S)-6-fluoro-2-[2-({3-[(2-fluoro-ethyl)-(3-methoxy-2-methoxymethyl-2-methyl-propyl)-amino]-propyl}-methyl-amino)-ethyl]-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-ol and 0.44 mL of NEt3 in 8 mL of DCM 0.25 mL of isobutyrylchloride was added at 0° C. The mixture was stirred for 25 min at 0° C. and then for 3 h at rt. It was quenched with sat. aqueous NaHCO3 and extracted with DCM. The organic phase was dried over anh. Na2SO4 and concentrated in vacuo. The resulting crude was purified by CC using EtOAc/Hept 3/1 as eluant to yield 411 mg of isobutyric acid (1S,2S)-6-fluoro-2-[2-({3-[(2-fluoro-ethyl)-(3-methoxy-2-methoxymethyl-2-methyl-propyl)-amino]-propyl}-methyl-amino)-ethyl]-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-yl ester as orange oil.

Workup

  1. waitfor 3 h at rt
  2. customIt was quenched with sat. aqueous NaHCO3
  3. extractionextracted with DCM
  4. dry with materialThe organic phase was dried over anh. Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe resulting crude was purified by CC

Sources & evidence

ORD record
ord-3e10451276e046b5b3e6d2be8a5add0b
Source dataset
uspto-grants-2013_05
Patent number
US08436205B2

Reaction notes

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