Acetonitrile → HCID 59378886, compound

HRID 1643913Notes

Reaction equation

Cl.[F:2][C:3]1[CH:4]=[C:5]([S:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:6]=[C:7]2[C:12]=1[C@H:11]([CH2:13][NH2:14])[CH2:10][CH2:9][CH2:8]2.C(#N)C.C(N(CC)CC)C.[C:32](OC(=O)C)(=[O:34])[CH3:33]>CN(C1C=CN=CC=1)C.O>[F:2][C:3]1[CH:4]=[C:5]([S:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:6]=[C:7]2[C:12]=1[C@H:11]([CH2:13][NH:14][C:32](=[O:34])[CH3:33])[CH2:10][CH2:9][CH2:8]2

Participants

Conditions

Temperature: 25 °C

Procedure

A mixture of C—((R)-8-fluoro-6-phenylsulfanyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-methylamine hydrochloride (1.36 kg), DMAP (10 g), acetonitrile (8.6 L), triethylamine (1.27 L), and acetic anhydride (0.41 L) was stirred at 25° C. After thirty minutes water (17.5 L) was added. The resulting slurry was stirred for 30 minutes at 25° C. The product was isolated by filtration and washed with 7.5 L of water. Drying overnight at 50° C. provided 1.34 kg of N—((R)-8-fluoro-6-phenylsulfanyl-1,2,3,4-tetrahydro-naphthalen-1-ylmethyl)-acetamide (97.4% yield, 99.66% pure by HPLC, 98.08% ee): MP=94.6-95.9° C.; MS (M+1)=330; H1 NMR (300 MHz): δ (DMSO): 1.44-1.91 (4H, m), 1.83 (3H, s), 2.54-2.79 (2H, m), 3.06 (1H, m), 3.16 (2H, m), 6.83 (1H, dd, =1.51, 10.17 Hz), 6.90 (1H, bs), 7.30-7.45 (5H, m, phenyl), 8.01 (1H, bt, J=5.65 Hz, NH); [α]D=7.4° (MeOH). Chiral Assay (Area Norm): Column: Chiralpak AD-H (150×4.6 mm), mobile phase 88/12 hexane/ethanol(isocratic) Flow rate 0.7 ml/min, 25° C., uv @230 nm.: (R)-isomer 99.04/(S)-isomer 0.96

Workup

stirringThe resulting slurry was stirred for 30 minutes at 25° C
customThe product was isolated by filtration
washwashed with 7.5 L of water
customDrying overnight at 50° C.

Sources & evidence

ORD record: ord-815cec59931b419488043a69c02ba048
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08119842B2

Reaction notes

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